A Weekly Combination of Topotecan & Docetaxel Produces Clinical Benefit In Heavily Pretreated Ovarian Cancer Patients

Recurrent and metastatic endometrial and ovarian cancers can be notoriously difficult to treat. … Physicians at the Albert Einstein College of Medicine of Yeshiva University showed that a combination of two chemotherapy drugs not only produced clinical benefit for such patients but were also well tolerated.  The results of this phase II study were published online in Gynecologic Oncology on March 21st. …[T]he researchers concluded that the combination of weekly topotecan and docetaxel has clinical benefit and is well tolerated in this heavily treated epithelial ovarian and uterine cancer patient population.  The researchers also noted that patients with platinum-resistant tumors had clinical benefit and should be considered for further study with this regimen. …

Recurrent and metastatic endometrial and ovarian cancers can be notoriously difficult to treat.  Both diseases are capable of  spreading to other organs and developing resistance to chemotherapy.  Typically, under this scenario, the patients have been heavily treated with chemotherapy and may not be able to endure additional treatment. Physicians at the Albert Einstein College of Medicine of Yeshiva University showed that a combination of two chemotherapy drugs not only produced clinical benefit for such patients but were also well tolerated.  The results of this phase II clinical study were published online in Gynecologic Oncology on March 21st.

Mark H. Einstein, M.D., M.S., Associate Professor of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine of Yeshiva University

“Women with recurrent gynecologic cancers have often had multiple rounds of chemotherapy, which can cause tumor cells to develop resistance to these drugs,” says Mark H. Einstein, M.D., M.S., Associate Professor of Obstetrics & Gynecology and Women’s Health at Einstein, who headed the study. “This resistance can make it difficult for doctors to devise a treatment protocol that will impact the cancers while avoiding the often-severe side effects that certain chemotherapy drugs can cause, particularly when patients have already been heavily pretreated with other anti-cancer drugs.”Under the trial protocol, eligible patients with recurrent epithelial ovarian or uterine cancers were treated with weekly topotecan 3.5 mg/m(2) and docetaxel 30 mg/m(2) for 3 consecutive weeks. Cycles were repeated every 4 weeks for 6 cycles or until evidence of disease progression or unacceptable toxicity. Patient response was assessed under Response Evaluation Criteria In Solid Tumors (RECIST) or, when appropriate, Rustin’s Criteria.  The majority of patients had received 2 prior chemotherapy regimens (9 pts had received 1 previous regimen, 16 pts. had received 2, 1 pt. had received 3, and 1 pt. had received 4).  Of the twenty-seven patients registered, 24 were evaluable for response.  The results of the trial are set forth below.

• 86 cycles of chemotherapy were administered.
• There were three grade 4 (all neutropenia) and ten grade 3 toxicities.Six of the grade 3 toxicities were unrelated to treatment.
• There were 8 dose delays and 4 dose reductions.
• The overall response rate was 25%  (8% CR, 17% PR).
• The clinical benefit rate was 38% (8% CR+17% PR+13% SD).
• The median duration of response was 8.5 months (range 3-19 months).
• The median overall survival was 18.5 months (range 1.8-50.7 months.

Based upon the foregoing results, the researchers concluded that the combination of weekly topotecan and docetaxel has clinical benefit and is well tolerated in this heavily treated epithelial ovarian and uterine cancer patient population.  The researchers also noted that patients with platinum–resistant tumors had clinical benefit and should be considered for further study with this regimen.Compared with previous clinical trials, an unusually high proportion of these women had been heavily pretreated with chemotherapy─yet nearly 40 percent of them experienced clinical benefit. In addition, the overall survival with the drug combination (median survival of 18.5 months) was higher than in previous phase II studies that evaluated the drugs on an individual basis.  Finally, there were few and relatively mild side effects from the drug combination compared with toxicities observed in similar studies.

The effectiveness and safety outcomes of the trial are “promising enough to justify a larger clinical study of this drug combination for women with recurrent gynecologic cancers,” Dr. Einstein said.

Other researchers at Einstein involved in the trial were Divya Gupta, M.D., Ricky L. Owers, M.D., Mimi Kim, Sc.D., Dennis Yi-Shin Kuo, M.D., Gloria S. Huang, M.D., Shohreh Shahabi, M.D., and Gary L. Goldberg, M.D. Dr. Einstein’s research was funded, in part, by investigator-initiated grants from Sanofi-Aventis and GlaxoSmithKline Oncology for research-related trial costs.

Sources:

• Gupta D, Owers RL, Kim M, et. al. A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers. Gynecol Oncol. 2009 Mar 21. [Epub ahead of print].  PMID: 19307014.

• New Treatment Shows Promise Against Recurrent Gynecologic Cancers, Einstein News, Albert Einstein College of Medicine of Yeshiva University, April 21, 2009.

M.D. Anderson Study Predicts Dramatic Growth in Cancer Rates Among U.S. Elderly, Minorities

” … Over the next 20 years, the number of new cancer cases diagnosed annually in the United States will increase by 45 percent, from 1.6 million in 2010 to 2.3 million in 2030, with a dramatic spike in incidence predicted in the elderly and minority populations, according to research from The University of Texas M. D. Anderson Cancer Center. …Given these statistics, the role of screening and prevention strategies becomes all the more vital and should be strongly encouraged, said [Ben] Smith [M.D.]. … These findings also highlight two issues that must be addressed simultaneously: clinical trial participation and the increasing cost of cancer care. Historically, both older adults and minorities have been under-represented in such studies, and, therefore, vulnerable to sub-optimal cancer treatment. Simultaneously, over the past decade in particular, the cost of cancer care is growing at a rate that’s not sustainable. …”

“Research underscores impact on health care system, importance of screenings, prevention strategies, inclusive clinical trials

Cancer Newsline Podcast
M. D. Anderson audio player (click & play)
Dramatic Growth in Cancer Rates Among Elderly, Minorities

Over the next 20 years, the number of new cancer cases diagnosed annually in the United States will increase by 45 percent, from 1.6 million in 2010 to 2.3 million in 2030, with a dramatic spike in incidence predicted in the elderly and minority populations, according to research from The University of Texas M. D. Anderson Cancer Center.

The study, published online today in Journal of Clinical Oncology, is the first to determine such specific long-term cancer incidence projections. It predicts a 67 percent increase in the number of adults age-65-or-older diagnosed with cancer, from 1 million in 2010 to 1.6 million in 2030. In non-white individuals over the same 20-year span, the incidence is expected to increase by 100 percent, from 330,000 to 660,000.

Ben Smith, M.D., Adjunct Assistant Professor, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center

According to Ben Smith, M.D., adjunct assistant professor in M. D. Anderson’s Department of Radiation Oncology, the study underscores cancer’s growing stress on the U.S. health care system.

‘In 2030, 70 percent of all cancers will be diagnosed in the elderly and 28 percent in minorities, and the number of older adults diagnosed with cancer will be the same as the total number of Americans diagnosed with cancer in 2010,’ said Smith, the study’s senior author. ‘Also alarming is that a number of the types of cancers that are expected to increase, such as liver, stomach and pancreas, still have tremendously high mortality rates.’

Unless specific prevention and/or treatment strategies are discovered, cancer death rates also will increase dramatically, said Smith, who is currently on active military duty and is stationed at Lackland Air Force Base.

To conduct their research, Smith and his team accessed the United States Census Bureau statistics, updated in 2008 to project population growth through 2050, and the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) registry, the premier population-based cancer registry representing 26 percent of the country’s population. Cancer incidence rates were calculated by multiplying the age, sex, race and origin-specific population projections by the age, sex, race and origin-specific cancer incidence rates.

The researchers found that from 2010 to 2030, the population is expected to grow by 19 percent (from 305 to 365 million). The total number of cancer cases will increase by 45 percent (from 1.6 to 2.3 million), with a 67 percent increase in cancer incidence in older Americans (1 to 1.6 million), compared to an 11 percent increase in those under the age of 65 (.63 to .67 million).

With respect to race, a 100 percent increase in cancer is expected for minorities (.33 to .66 million); in contrast, in white Americans, a 31 percent increase is anticipated (1.3 to 1.7 million). The rates of cancer in blacks, American Indian-Alaska Native, multi-racial, Asian-Pacific Islanders and Hispanics will increase by 64 percent, 76 percent, 101 percent, 132 percent and 142 percent, respectively.

Regarding disease-specific findings, Smith and his team found that the leading cancer sites are expected to remain constant – breast, prostate, colon and lung. However, cancer sites with the greatest increase in incidence expected are: stomach (67 percent); liver (59 percent); myeloma (57 percent); pancreas (55 percent); and bladder (54 percent).

Given these statistics, the role of screening and prevention strategies becomes all the more vital and should be strongly encouraged, said Smith. In the study, Smith and his team site [sic]: vaccinations for hepatitis B and HPV; the chemoprevention agents tamoxifen and raloxifene; interventions for tobacco and alcohol; and removal of pre-malignant lesions, such as colon polyps.

These findings also highlight two issues that must be addressed simultaneously: clinical trial participation and the increasing cost of cancer care. Historically, both older adults and minorities have been under-represented in such studies, and, therefore, vulnerable to sub-optimal cancer treatment. Simultaneously, over the past decade in particular, the cost of cancer care is growing at a rate that’s not sustainable.

‘The fact that these two groups have been under-represented in clinical research participation, yet their incidence of cancer is growing so rapidly, reflects the need for therapeutic trials to be more inclusive and address issues that are particularly relevant to both populations,’ said Smith. ‘In addition, as we design clinical trials, we need to seek not only the treatment that will prolong survival, but prolong survival at a reasonable cost to patients. These are two issues that oncologists need to be much more concerned about and attuned to.’

Another issue that needs to be addressed is the shortage of health care professionals predicted. For example, according to a workforce assessment by American Society for Clinical Oncology (ASCO), the shortage of medical oncologists will impact the health care system by 2020. Smith said ASCO and other professional medical organizations beyond oncology are aware of the problem, and are actively engaged in efforts to try and grow the number of physicians, as well as encourage the careers of nurse practitioners and physician assistants who are part of the continuum of care, to best accommodate the increase in demand forecasted.

‘There’s no doubt the increasing incidence of cancer is a very important societal issue. There will not be one solution to this problem, but many different issues that need to be addressed to prepare for these changes,’ said Smith. ‘I’m afraid if we don’t come to grips with this as a society, health care may be the next bubble to burst.’

In addition to Smith, other M. D. Anderson authors on the study include: Thomas Buchholz, M.D., professor and chair of the Department of Radiation Oncology and the study’s senior author; Gabriel Hortobagyi, M.D., professor and chair of the Department of Breast Medical Oncology; and Grace Smith, M.D., Ph.D., assistant professor in the Department of Radiation Oncology. Arti Hurria, M.D., post-doctoral fellow in the Department of Medical Oncology, City of Hope Cancer Center, also is a contributing author on the study.”

Sources:

• M. D. Anderson Study Predicts Dramatic Growth in Cancer Rates Among U.S. Elderly, Minorities – Research underscores impact on health care system, importance of screenings, prevention strategies, inclusive clinical trials, News Release, The University of Texas M.D. Anderson Cancer Center, April 29, 2009.

• Smith BD, Smith GL, Hurria A, Hortobagyi GA, Buchholz TA. Future of Cancer Incidence in the United States: Burdens Upon an Aging, Changing Nation. J Clin Oncol 2009 0: JCO.2008.20.8983, published online ahead of print Apr 29 2009.

Women of Diverse Ethnic Ancestry Have Similar Risk of Carrying BRCA Mutations as Those With Western European Ancestry

” …The study, performed by researchers at Philadelphia’s Fox Chase Cancer Center and Myriad Genetics, Inc., analyzed the prevalence of BRCA1/BRCA2 gene mutations in patients of different ethnicities at risk for hereditary breast and ovarian cancer. The study included test results of 46,276 women during the ten-year period from 1996 to 2006. Study subjects encompassed a broad, diverse ethnic group, including individuals of European, Latin American, African, Asian and Native American ancestries. … Results of the study showed that BRCA disease-causing mutations were identified in 5,780 women tested (12.5%) across all ethnic populations. Importantly, the study demonstrated that individuals of African and Latin American ancestry had as great a risk in having BRCA mutations as women with western European ancestry, when controlled for the level of personal and family history of breast and ovarian cancer. …”

“New Study Published in CANCER Supports Use of BRACAnalysis Testing Across Broad Ethnic Populations

Women of Asian, African and Latin American Ancestry Had Similar Risk of Carrying BRCA Mutations as Those With Western European Ancestry

SALT LAKE CITY, UT, Apr 30, 2009 (MARKET WIRE via COMTEX News Network) — Myriad Genetics, Inc. (NASDAQ: MYGN) announced today that an article entitled ‘BRCA1 and BRCA2 Mutations in Women of Different Ethnicities Undergoing Testing for Hereditary Breast-Ovarian Cancer‘ will appear in the May 15, 2009 issue of the journal CANCER.  The study demonstrates that BRACAnalysis(R) testing of at-risk women across diverse ethnicities helps identify individuals who may benefit from improved surveillance, medical and surgical strategies to reduce their hereditary cancer risks.

Gregory C. Critchfield, M.D., M.S., President, Myriad Genetic Laboratories

‘This study, the largest of its kind, shows convincingly that strong family or personal history of breast or ovarian cancer is associated with a high prevalence of BRCA mutations — irrespective of one’s ethnic heritage,’ stated Gregory C. Critchfield, M.D., M.S., President of Myriad Genetic Laboratories.

The association between ethnicity and the risk of BRCA1 or BRCA2 mutations has not been well understood in women of non-European ancestry. This study provides important information for women of Asian, African, Latin American and Native American ancestry that may impact breast cancer [and ovarian cancer] prevention and treatment efforts among women in these populations. The study, performed by researchers at Philadelphia’s Fox Chase Cancer Center and Myriad Genetics, Inc., analyzed the prevalence of BRCA1/BRCA2 gene mutations in patients of different ethnicities at risk for hereditary breast and ovarian cancer. The study included test results of 46,276 women during the ten-year period from 1996 to 2006. Study subjects encompassed a broad, diverse ethnic group, including individuals of European, Latin American, African, Asian and Native American ancestries. To date, this work represents the largest group of patients tested for BRCA mutations reported in the literature. All testing was performed at Myriad Genetics, Inc.

Results of the study showed that BRCA disease-causing mutations were identified in 5,780 women tested (12.5%) across all ethnic populations. Importantly, the study demonstrated that individuals of African and Latin American ancestry had as great a risk in having BRCA mutations as women with western European ancestry, when controlled for the level of personal and family history of breast and ovarian cancer.

Professional medical society guidelines, such as the American Society of Clinical Oncologists (ASCO), the Society of Gynecologic Oncologists (SGO), and the American College of Obstetricians and Gynecologists (ACOG), articulate risk factors for BRCA gene mutations, which include, among others, breast cancer occurring before age 50, personal or family history of ovarian cancer at any age, personal or family history of male breast cancer, Ashkenazi Jewish ancestry with breast cancer at any age, or the presence of a known BRCA mutation in the family.

About BRACAnalysis(R)

BRACAnalysis(R) is a comprehensive analysis of the BRCA1 and BRCA2 genes for assessing a woman’s risk for breast and ovarian cancer. A woman who tests positive with the BRACAnalysis(R) test has, on average, an 82% lifetime risk of developing breast cancer during her lifetime and a 44% risk of developing ovarian cancer. BRACAnalysis(R) provides important information that the Company believes will help the patient and her physician make better informed lifestyle, surveillance, preventive medication and treatment decisions. As published in the Journal of the National Cancer Institute, researchers have shown that pre-symptomatic individuals who have a high risk of developing breast cancer can reduce their risk by approximately 50% with appropriate preventive therapies. Additionally, as published in the New England Journal of Medicine, researchers have shown that pre-symptomatic individuals who carry gene mutations can lower their risk of developing ovarian cancer by approximately 60% with appropriate preventive therapies.

For more information about BRACAnalysis(R), please call 1-800-4-MYRIAD, or visit www.myriadtests.com.

About Myriad Genetics

Myriad Genetics, Inc. is a leading healthcare company focused on the development and marketing of novel molecular diagnostic and therapeutic products. Myriad’s news and other information are available on the Company’s Web site at www.myriad.com.

Myriad, the Myriad logo, BRACAnalysis, Colaris, Colaris AP, Melaris, TheraGuide, Prezeon, OnDose, Azixa and Vivecon are trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and foreign countries. MYGN-G”

Sources: 

• New Study Published in CANCER Supports Use of BRACAnalysis Testing Across Broad Ethnic Populations – Women of Asian, African and Latin American Ancestry Had Similar Risk of Carrying BRCA Mutations as Those With Western European Ancestry, Press Release, Myriad Genetics Inc., April 30, 2009.

• Hall MJ, Reid JE, Burbidge LA  et. al. BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast-ovarian cancer. Cancer. 2009; 115(10):2222-2233.  doi: 10.1002/cncr.24200

Related Information:  CLICK HERE to review all Libby’s H*O*P*E*™ postings relating to BRCA gene mutations.

Preclinical Results Validate Lpathomab As A Potential Future Treatment for Ovarian Cancer

“Lpath, Inc. … , the category leader in bioactive-lipid-targeted therapeutics, reported compelling new in vivo and in vitro results relating to its preclinical drug candidate, Lpathomab, in various ovarian cancer studies …”

“Lpath Presents Compelling New Preclinical Results of Its Anti-Cancer Drug Candidate, Lpathomab(TM), at the AACR 100th Annual Meeting –

New In Vivo and In Vitro Results Provide Further Validation of Lpathomab as Potential Treatment for Cancer

SAN DIEGO, CA, Apr 20, 2009 (MARKET WIRE via COMTEX) — Lpath, Inc. (OTCBB: LPTN), the category leader in bioactive–lipid-targeted therapeutics, reported compelling new in vivo and in vitro results relating to its preclinical drug candidate, Lpathomab, in various ovarian cancer studies. The results were presented today by Lpath scientists at the 100th Annual Meeting of the American Association for Cancer Research (AACR) in Denver, Colorado.

Lpathomab is a monoclonal antibody that binds to the bioactive lipid lysophosphatidic acid (LPA) and acts as a molecular sponge to absorb LPA, thereby neutralizing LPA-mediated biological effects on tumor growth, angiogenesis, and metastasis. LPA has been associated with a variety of cancer types, but the correlation with ovarian cancer and breast cancer has been particularly strong.

Using the human ovarian cell line called SKOV3, Lpath’s preclinical studies demonstrated Lpathomab significantly reduced IL-8 and IL-6 cytokine release in SKOV3-conditioned media and blocked tumor-cell migration triggered by LPA (both IL-8 and IL-6 promote tumor angiogenesis and metastasis). More important, Lpathomab inhibited the progression of SKOV3 tumor cells when injected into the peritoneal cavity of mice and reduced levels of pro-metastatic factors in these animals.

Lpathomab also reduced neovascularization (new blood-vessel growth) in two classical angiogenic models and showed preliminary anti-metastatic activity when tested in a classical experimental metastasis model.

According to Roger Sabbadini, Ph.D., Lpath’s founder and chief scientific officer, ‘In view of these promising preclinical results, we believe Lpathomab has the potential to augment the efficacy of current ovarian cancer therapy by blocking the growth-promoting, angiogenic, and metastatic effects of LPA.’

About Lpath

San-Diego-based Lpath, Inc. is the category leader in bioactive-lipid-targeted therapeutics, an emerging field of medical science whereby bioactive signaling lipids are targeted for treating important human diseases. ASONEP(TM), an antibody against Sphingosine-1-Phosphate (S1P), is currently in a Phase 1 clinical trial in cancer patients and also holds promise against multiple sclerosis and various other disorders. ASONEP is being developed with the support of partner Merck-Serono as part of a worldwide exclusive license. A second product candidate, iSONEP(TM) (the ocular formulation of the S1P antibody), has demonstrated superior results in various preclinical models of age-related macular degeneration (AMD) and retinopathy and is in a Phase 1 clinical trial in wet-AMD patients. Lpath’s third product candidate, Lpathomab(TM), is an antibody against lysophosphatidic acid (LPA), a key bioactive lipid that has been long recognized as a valid disease target (cancer, neuropathic pain, fibrosis). The company’s unique ability to generate novel antibodies against bioactive lipids is based on its ImmuneY2(TM) drug-discovery engine, which the company is leveraging as a means to expand its pipeline. For more information, visit www.Lpath.com …”

Sources:

• Lpath Presents Compelling New Preclinical Results of Its Anti-Cancer Drug Candidate, Lpathomab(TM), at the AACR 100th Annual Meeting – New In Vivo and In Vitro Results Provide Further Validation of Lpathomab as Potential Treatment for Cancer, News Releases, Lpath Incorporated, April 20, 2009.

• Visentin B, Gentile AM, Matteo R, Tripple V, Nguyen K, Moreno KM et. al. In vitro and in vivo efficacy of Lpathomab™, a monoclonal antibody directed against lysophosphatidic acid (LPA), in ovarian cancer models. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract 1247

Novogen’s NV-128 Targets mTOR Pathway To Block Differentiation and Induce Cell Death in Ovarian Cancer Stem Cells

“Data just presented at the Annual Meeting of the American Association for Cancer Research in Denver has demonstrated that NV-128, a Novogen, Limited (ASX: NRT NASDQ: NVGN) synthetic isoflavonoid compound, not only induces cell death in Ovarian Cancer Stem Cells (OCSCs), but also blocks their differentiation into structures which are required to support tumor growth.  In a poster presentation by Ayesha Alvero, MD, of Yale University School of Medicine, Department of Obstetrics, Gynecology and Reproductive Science, it was revealed that in addition to an inhibitory effect on OCSC growth, NV-128 displays a remarkable ability to inhibit differentiation of OCSCs into formation of new blood vessels. … ‘We have now demonstrated that by inhibiting the mTOR pathway in both the cancer stem cells and the mature cancer cells, we are able to inhibit development of structural elements necessary for tumor development as well as limit the number of cancer cells,’ Professor Mor said. ‘These results open a new avenue for the development of better treatment modalities for ovarian cancer patients.’ …”

“(Sydney Australia and New Canaan, Connecticut – 20 April, 2009) – Data just presented at the Annual Meeting of the American Association for Cancer Research in Denver has demonstrated that NV-128, a Novogen, Limited (ASX: NRT NASDQ: NVGN) synthetic isoflavonoid compound, not only induces cell death in Ovarian Cancer Stem Cells (OCSCs), but also blocks their differentiation into structures which are required to support tumor growth.

Ayesha Alvero, M.D., Associate Research Fellow, Department of Obstetrics, Gynecology and Reproductive Science, Yale University School of Medicine

In a poster presentation by Ayesha Alvero, MD, of Yale University School of Medicine, Department of Obstetrics, Gynecology and Reproductive Science, it was revealed that in addition to an inhibitory effect on OCSC growth, NV-128 displays a remarkable ability to inhibit differentiation of OCSCs into formation of new blood vessels.

The anti-proliferative effects were demonstrated to be achieved as a result of NV-128 inhibiting phosphorylation of the pro-survival mTOR pathway resulting in mitochondrial depolarisation and cell death. Time lapsed photographic morphometry revealed in graphic detail how NV-128 induces morphological changes in OCSCs after 24 hours, even when dosed as low as 1μg/ml with a progressive “clearing” of cytoplasm and condensation of nuclear material.

The effect of NV-128 on OCSC vessel formation was observed by plating OCSCs in high-density matrigel either without NV-128 (controls) or in the presence of 0.1 mg/ml NV-128 and observing for 48 hours. Whereas the control cultures showed differentiation of the stem cells into endothelial-type cells forming structurally intact blood vessels in the culture plates, cells cultured in the presence of NV-128 showed no differentiation and no structural elements were observed.

OCSCs represent a highly chemo-resistant cell population, allowing them to survive conventional chemotherapy. Thus these cells are considered to be the potential source of tumor induction and post-treatment recurrence.

The team from Yale University, headed by Professor Gil Mor, recently reported the identification and characterisation of OCSCs using the CD44 marker and demonstrated pronounced up-regulation of the mTOR survival pathway in these cells. They previously reported that NV-128 is able to specifically induce mTOR dephosphorylation resulting in inhibition of both mTORC1 and mTORC2 activity in mature ovarian cancer cells derived from established human cancers and cultured in vitro. In mice with human ovarian cancers established by grafting techniques (xenografts) NV-128 caused substantial cancer cell death, reducing tumor growth with no apparent toxic side-effects.

Gil Mor, M.D., Ph.D., Associate Professor, Department of Obstetrics, Gynecology and Reproductive Science, Yale University School of Medicine

‘We have now demonstrated that by inhibiting the mTOR pathway in both the cancer stem cells and the mature cancer cells, we are able to inhibit development of structural elements necessary for tumor development as well as limit the number of cancer cells,’ Professor Mor said. ‘These results open a new avenue for the development of better treatment modalities for ovarian cancer patients.’

‘We are encouraged by these data from animal studies showing a combination of anti-cancer activities of NV-128, coupled with an apparently high safety profile,’ said Professor Alan Husband, Group Director of Research for the Novogen group. ‘This anti-angiogenic effect, coupled with the absolute effects on cell survival, demonstrate the potential for NV-128 to become a powerful new tool in prevention as well as treatment of cancer.’

Novogen has previously reported on the parallel effects of NV-128 in non-small cell lung cancer models and the Company intends to pursue this, as well as ovarian cancer, as target indications.

Novogen is currently in advanced negotiations with its majority owned subsidiary, Marshall Edwards, Inc. (MEI), to out-license NV-128 to MEI for its clinical development as a potential cancer therapeutic. To view an online abstract relating to this study, [CLICK HERE].

About NV-128

NV-128 does not rely on the traditional approach of caspase-mediated apoptosis, a death mechanism which is not effective in cancer cells that have become resistant to chemotherapy. Rather, NV-128 uncouples a signal transduction cascade which has a key role in driving protein translation and uncontrolled cancer cell proliferation. Further, NV-128 induces mitochondrial depolarisation via the novel mTOR pathway. In cancer cells, mTOR signals enhance tumor growth and may be associated with resistance to conventional therapies. Inhibition of the mTOR pathway appears to shut down many of these survival pathways, including proteins that protect the mitochondria of cancer cells. Animal studies have shown that NV-128 not only significantly retards tumor proliferation, inhibiting the progression of ovarian cancers-engrafted into mice, but produces this effect without apparent toxicity. This effect was shown to be due to caspase-independent pathways involving inhibition of the mTOR pathway. Unlike analogues of rapamycin, which target only mTORC1, NV-128’s capacity to inhibit mTOR phosphorylation enables it to inhibit both mTORC1 and mTORC2 activity. This blocks growth factor-driven activation of AKT and the potential for development of chemoresistance.

About Novogen Limited

Novogen Limited (ASX: NRT; NASDAQ: NVGN) is an Australian biotechnology company based in Sydney, Australia, that is developing a range of oncology therapeutics from its proprietary flavonoid synthetic chemistry technology platform. More information on NV-128 and on the Novogen group of companies can be found at www.novogen.com.

Sources:

• Novengen’s NV-128 Targets mTOR Pathway To Block Differentiation, ASX News Release, Novogen, Ltd., April 20, 2009.

• Mor GG, Alvero AB, Montagna MK, Brown DM, Husband AJ. NV-128, a novel isoflavone derivative, targets the mTOR pathway and induces cell death in epithelial ovarian cancer stem cells. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract 1841.

Additional Information Re Novogen’s NV-128:

• Novogen’s NV-128 blocks differentiation in cancer stem cells, Audio Webcast, Professor Alan Husband, Director of Research, Novogen Group, The Australian Business with the Wall Street Journal, April 20, 2009.

• Ovarian Cancer Stem Cells Identified, Characterized, Science News, Science Daily, April 18, 2008.

• Yale Researchers Indicate That Novogen Compound NV-128 Induces Cell Death in Chemo-Resistant Ovarian Cancer Cells, by Paul Cacciatore, Libby’s H*O*P*E*™, March 26, 2008.

Personalized Medicine Helps Breast, Colorectal & Ovarian Cancer Patients Survive

“Cancer patients can survive longer under treatments based on their individual genetic profiles, according to a nationwide study released jointly today by Phoenix-area healthcare organizations. The study shows that molecular profiling of patients can identify specific treatments for individuals, helping keep their cancer in check for significantly longer periods, and in some cases even shrinking tumors. Study results were released today at the 100th annual meeting of the American Association for Cancer Research in Denver by Dr. Daniel Von Hoff, Physician-In-Chief of the Phoenix-based Translational Genomics Research Institute (TGen), and the study’s Principal Investigator. … Patients experienced varying levels of improvement. Among those with breast cancer, the period of progression-free survival increased for 44 percent of patients; for colorectal, 36 percent of patients; for ovarian, 20 percent of patients; and for miscellaneous cancers the improvement was seen in 16 percent of patients. …” [Emphasis added by Libby’s H*O*P*E*™]

“Personalized medicine helps cancer patients survive – TGen, Scottsdale Healthcare and Caris Dx clinical trial shows molecular profiling can result in specific treatments for individual patients that significantly limit the growth and spread of tumors

PHOENIX, Ariz. – April 19, 2009 – Cancer patients can survive longer under treatments based on their individual genetic profiles, according to a nationwide study released jointly today by Phoenix-area healthcare organizations.

The study shows that molecular profiling of patients can identify specific treatments for individuals, helping keep their cancer in check for significantly longer periods, and in some cases even shrinking tumors.

Daniel Von Hoff, M.D., F.A.C.P., Physician in Chief & Senior Investigator, The Translational Genomics Research Institute; Chief Scientific Officer, TGen Clinical Research Services, Scottsdale Healthcare; Clinical Professor of Medicine, University of Arizona Department of Medicine

Study results were released today at the 100th annual meeting of the American Association for Cancer Research in Denver by Dr. Daniel Von Hoff, Physician-In-Chief of the Phoenix-based Translational Genomics Research Institute (TGen), and the study’s Principal Investigator.

The study included 66 patients at nine centers across the United States, including Scottsdale Heathcare. Dr. Von Hoff also is the Chief Scientific Officer of TGen Clinical Research Services (TCRS) at Scottsdale Healthcare, a partnership between TGen and Scottsdale Healthcare that is administered by the Scottsdale Clinical Research Institute (SCRI) at Scottsdale Healthcare.

All of the patients had previously experienced growth of their tumors while undergoing as many as two to six prior cancer treatments, including conventional chemotherapy.

However, after molecular profiling identified precise targets, new treatments were administered that resulted in patients experiencing significant periods of time when there was no progression of their cancer.

‘This clinical trial was unique because patients acted as their own control,’ said Dr. Von Hoff. ‘We compared each patient’s progression-free survival, following treatment based on molecular profiling, to how their tumors progressed under their prior treatment regimens, before molecular profiling.’

In a significant number of patients, the targeted treatments provided significantly longer periods when tumors did not progress, or even shrunk, said Dr. Von Hoff, who also is a Medical Director of US Oncology and a former Director of the Arizona Cancer Center at the University of Arizona.

Dr. Von Hoff said the new study was done in a way that avoided issues surrounding tumor subtypes and differences in individual biology, which have confounded other clinical trials.

He said this clinical trial demonstrated the value of personalized medicine, in which treatments are prescribed based on an individual’s specific genetic makeup. The type of drugs, dosages, their delivery and other treatment aspects – all are based on each patient’s individual medical needs.

Among the patients, 27 percent had breast cancer, 17 percent had colorectal cancer, 8 percent had ovarian cancer and 48 percent had cancers that were classified as miscellaneous.

Patients experienced varying levels of improvement. Among those with breast cancer, the period of progression-free survival increased for 44 percent of patients; for colorectal, 36 percent of patients; for ovarian, 20 percent of patients; and for miscellaneous cancers the improvement was seen in 16 percent of patients.

‘With this trial, we are showing the power of personalized medicine using the tools we already have available to us. As these tools become more precise and more effective, the value of personalized medicine will increase,’ Dr. Von Hoff said.

The molecular profiling for this research study was performed by Caris Diagnostics (Caris Dx) in Phoenix.

These results are the first in a series of studies in support of Target Now^TM, a commercially-available oncology testing service offered exclusively by Caris Dx. Target Now uses cutting-edge molecular profiling techniques, including both DNA microarray and immunohistochemical (IHC) analysis, to provide individualized information about a patient’s tumor as an aid to the treating oncologist.

‘This trial is evidence of an important breakthrough in the treatment of cancer. We are excited to work with Dr. Von Hoff and TGen as we make this important molecular diagnostic information available to physicians to aid in therapy-selection decision making,’ said David D. Halbert, Chairman and CEO of Caris Diagnostics. ‘The valuable information provided through the Target Now panel of tests improves patient care while reducing costs for the payer.’

Clinical studies were conducted by TCRS at the Virginia G. Piper Cancer Center at Scottsdale Healthcare Shea Medical Center. Scottsdale Healthcare is a primary clinical research site for TGen.

‘Patients in our community have access to ground-breaking, world-class research right in their own backyard thanks to this collaboration,’ said Tom Sadvary, president and CEO of Scottsdale Healthcare. ‘Our goal is reducing the time it takes to get new treatment discoveries from the research lab to the patient. We are thrilled to see these advances in personalized medicine taking place right here in Scottsdale.’

The recent clinical study was dubbed the Bisgrove Trial, after longtime Scottsdale Healthcare supporter Jerry Bisgrove. The trial was funded through a $5 million grant from Mr. Bisgrove’s Stardust Foundation to the Scottsdale Healthcare Foundation. Mr. Bisgrove has been a patient at Scottsdale Healthcare and is a member of the Scottsdale Healthcare Foundation Board of Trustees. In honor of the Stardust gift, the research building at the Virginia G. Piper Cancer Center at Scottsdale Healthcare Shea Medical Center is named the Debi and Jerry Bisgrove Research Pavilion.

‘The Stardust Foundation is proud to have played a key role in the advancements in cancer research represented by Dr. Von Hoff’s clinical trial. We believe we are closer than ever to finding a cure for this devastating disease that affects so many millions,’ Mr. Bisgrove said.

*          *          *

About Scottsdale Healthcare
Scottsdale Healthcare is a primary clinical research site for TGen. TGen Clinical Research Services (TCRS) at Scottsdale Healthcare is housed in the Virginia G. Piper Cancer Center at Scottsdale Healthcare, located on the Scottsdale Healthcare Shea medical campus. Scottsdale Healthcare is the not-for-profit parent organization of the Scottsdale Healthcare Shea, Scottsdale Healthcare Osborn and Scottsdale Healthcare Thompson Peak hospitals, Virginia G. Piper Cancer Center, Scottsdale Clinical Research Institute, TGen Clinical Research Services at Scottsdale Healthcare, Scottsdale Healthcare Home Health Services, Scottsdale Healthcare Community Health Services, and Scottsdale Healthcare Foundation. For additional information, visit www.shc.org.

About Scottsdale Clinical Research Institute (SCRI)
SCRI, established in 2005, provides infrastructure and support for the clinical research at Scottsdale Healthcare. Start-up funding for SCRI was provided by a lead gift of $4.5 million from the Virginia G. Piper Charitable Trust in 2005. An additional $5 million was provided by the Stardust Foundation to support this multi-site molecular profiling study of targeted therapies for treatment refractory cancers coordinated by SCRI. A defining feature of SCRI is a focus on genomics and personalized medicine as well as clinical and translational research. The basic science arm of SCRI is provided by a partnership with the Translational Genomics Research Institute (TGen). Innovations from TGen’s laboratory are taken to the bedside at SHC by our joint clinical research program, TGen Clinical Research Services (TCRS) at Scottsdale Healthcare. Additional research collaborations include the University of Arizona, Arizona State University, other local health care delivery systems and participation in the Arizona NIH Clinical and Translational Science Award (CTSA) program initiative. Areas of study at SCRI include Cancer, Cardiovascular, Trauma, Metabolic and Nanomedicine.

Press Contact:
Keith Jones
Public Relations Director
Scottsdale Healthcare
480-882-4412
kjones@shc.org

About TGen
The Translational Genomics Research Institute (TGen) is a non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. For more information, visit: www.tgen.org.

Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
syozwiak@tgen.org

About Caris Diagnostics
Caris Diagnostics (Caris Dx) is a leading provider of the highest quality diagnostic, translational development and pharmaceutical services encompassing anatomic pathology and molecular testing. Caris Diagnostics provides world-class pathology services to physicians who treat patients in the community setting. The company provides academic-caliber medical consults through its industry-leading team of subspecialty fellowship and expert-trained pathologists in gastrointestinal and liver pathology, dermatopathology and hematopathology. Caris Diagnostics provides the highest levels of service to its customers and their patients through its state-of-the-art laboratories; proprietary, advanced clinical and technology solutions; and rigorous quality assurance programs. Through the molecular testing expertise of the Caris Molecular Profiling Institute (Caris MPI) at Caris Dx, the company also offers advanced molecular analyses of patient samples through prognostic testing services and genomic and proteomic profiling to provide critical information to physicians treating cancer and other complex diseases. In addition, Caris MPI supports pharmaceutical companies and other researchers in their clinical trials for targeted therapeutics with custom genomic and proteomic analyses, analyte preservation, tissue procurement and comprehensive reporting services. The company has strategic relationships with the International Genomics Consortium, US Oncology, the Translational Genomics Research Institute, and the Biodesign Institute of Arizona State University. More than 2,000 physicians nationally use Caris Diagnostics. Formed in 1996, the company is headquartered in Irving, Texas and operates four laboratories: Irving, Texas; Phoenix, Arizona (2 sites); Newton, Massachusetts. Additional information is available at www.carisdx.com.

Press Contact:
Brian Wright
Caris Dx
(602) 358-8916
bwright@carismpi.com”

Sources:

• Personalized medicine helps cancer patients survive – TGen, Scottsdale Healthcare and Caris Dx clinical trial shows molecular profiling can result in specific treatments for individual patients that significantly limit the growth and spread of tumors, News, The Translational Genomics Research Institute, April 19, 2009 [emphasis added by Libby’s H*O*P*E*™].

• Von Hoff DD, Stephenson Jr. JJ, Rosen PJ, Loesch DM, Borad MJ, Anthony SP, et. al. A pilot study utilizing molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract LB-259.

• A Pilot Study Utilizing Molecular Profiling of Patients’ Tumors to Find Potential Targets and Select Treatments for Their Refractory Cancers, Scottsdale Healthcare & Translational Genomics Research Institute, Clinical Trial Protocol Summary, National Institutes of Health, http://www.ClinicalTrials.gov (NCT00530192) [trial is recruiting as of this writing].

Genetic Variations In miRNA Processing Pathway & Binding Sites Help Predict Ovarian Cancer Risk

“Genetic variations in the micro-RNA (miRNA) processing pathway genes and miRNA binding sites predict a woman’s risk for developing ovarian cancer and her prospects for survival, researchers from The University of Texas M. D. Anderson Cancer Center reported at the 100th annual meeting of the American Association for Cancer Research. … The unique study was the first to examine the association of genetic variants related to miRNA with ovarian cancer risk, overall survival for ovarian cancer patients, and platinum-based chemotherapy response. …”

“Genetic variations in miRNA processing pathway and binding sites help predict ovarian cancer risk – Several variations indicate likelihood of response to platinum-based chemotherapy

DENVER – Genetic variations in the micro-RNA (miRNA) processing pathway genes and miRNA binding sites predict a woman’s risk for developing ovarian cancer and her prospects for survival, researchers from The University of Texas M. D. Anderson Cancer Center reported at the 100th annual meeting of the American Association for Cancer Research.

Xifeng Wu, M.D., Ph.D., Professor, Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center

‘We found a gene dosage effect, the more unfavorable variations a woman has, the greater her ovarian cancer risk and the shorter her survival time,’ said senior author Xifeng Wu, M.D., Ph.D., professor in M. D. Anderson’s Department of Epidemiology. Median survival, for example, ranged from 151 months for women with fewest unfavorable variations to 24 months for those with the most.

Several variations also indicate likely response to platinum-based chemotherapy.

‘Our findings have the potential clinical application of indicating a patient’s prognosis and showing who will respond to different therapies by analyzing a single blood sample,’ Wu said. ‘We also will incorporate this genetic information with epidemiological information to build a comprehensive model to predict susceptibility to ovarian cancer.’

The team chose the miRNA processing pathway because it is crucial to production of miRNAs, the small molecules that regulate between one third and half of all genes. The researchers also chose the binding sites on host genes where miRNAs exert their effects on gene expression.

They analyzed 219 potential functional single nucleotide polymorphisms (SNPs) – variations of a single DNA building block in a gene – in eight genes that process miRNA and at the miRNA binding sites of 129 cancer-relevant genes. The study examined genetic information from 417 cancer patients and 417 healthy controls. To minimize the possible confounding effects of ethnicity, 339 Caucasian cases and 349 controls were analyzed.

They discovered 12 SNPs to be significantly associated with ovarian cancer risk. Moreover, compared to women with five or fewer unfavorable genotypes, women with eight or more of these unfavorable genotypes were 4.5 times more likely to develop ovarian cancer and women with six to eight unfavorable SNPs were at twice the risk.

The team also found 21 SNPs significantly associated with overall survival. Median survival was 151 months for women with six or fewer unfavorable variations; 42 months for those with seven to nine unfavorable variations; and 24 months for those with 10 or more. One of the outcome risk SNPs also was strongly associated with platinum-based chemotherapy response, with those having the SNP 3.4 times less likely to respond to chemotherapy.

Wu collaborated with Dong Liang, Ph.D, in the College of Pharmacy and Health Sciences, Texas Southern University, and Karen Lu, M.D., professor in M. D. Anderson’s Department of Gynecologic Oncology, on this study.

The unique study was the first to examine the association of genetic variants related to miRNA with ovarian cancer risk, overall survival for ovarian cancer patients, and platinum-based chemotherapy response. Such a wide-ranging inquiry was made possible by M. D. Anderson’s extensive clinical and genetic data sets, Wu said.

Co-authors with Wu, first author Liang, Ph.D., and Lu are; Jie Lin, Ph.D., Xia Pu, Yuanqing Ye, Ph.D., all in the Department of Epidemiology; and Larissa Meyer, M.D., in the Department of Gynecologic Oncology at M. D. Anderson Cancer Center. Pu is a graduate student at The University of Texas Graduate School of Biomedical Sciences at Houston, which is a joint effort of M. D. Anderson and The University of Texas Health Science Center at Houston.

This research was supported by an award by the Department of Defense Ovarian Cancer Research Program.”

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For four of the past six years, including 2008, M. D. Anderson has ranked No. 1 in cancer care in “America’s Best Hospitals,” a survey published annually in U.S. News & World Report.

Sources:

• Genetic Variations in miRNA Processing Pathway and Binding Sites Help Predict Ovarian Cancer Risk and Survival – Several variations indicate likelihood of response to platinum-based chemotherapy, News Releases, The University of Texas M.D. Anderson Cancer Center, April 19, 2009.

• Liang D, Meyer L, Lin J, Pu X, Ye Y, Wu L, Lu K, Wu X. Genetic variants in microRNA processing pathway genes and ovarian cancer risk. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract 1905.

• Gene Variations Could Predict Ovarian Cancer Risk, Video News Story By Elizabeth Cohen, CNN, April 20, 2009.

Addition of Dasatinib (Sprycel) to Standard Chemo Cocktail May Enhance Effect in Certain Ovarian Cancers

“The addition of a chemotherapeutic drug for leukemia to a standard regimen of two other chemotherapy drugs appears to enhance the response of certain ovarian cancers to treatment, according to a pre-clinical study led by researchers in the Duke Comprehensive Cancer Center.  ‘We know that a pathway called SRC is involved in cell proliferation in certain types of cancers, including some ovarian cancers,’ said Deanna Teoh, MD, a fellow in gynecologic oncology at Duke and lead investigator on this study.  ‘By examining gene expression data, we determined that the combination of the leukemia drug dasatinib (Sprycel) made carboplatin and paclitaxel more effective in cell lines with higher levels of SRC expression and SRC pathway deregulation.’ …”

Angeles Secord, MD, Gynecologic Oncologist, Duke University Medical Center & Senior Investigator on this study. Deanna Teoh, MD, Gynecologic Oncologist at Duke was the lead investigator.

“The addition of a chemotherapeutic drug for leukemia to a standard regimen of two other chemotherapy drugs appears to enhance the response of certain ovarian cancers to treatment, according to a pre-clinical study led by researchers in the Duke Comprehensive Cancer Center.

‘We know that a pathway called SRC is involved in cell proliferation in certain types of cancers, including some ovarian cancers,’ said Deanna Teoh, MD, a fellow in gynecologic oncology at Duke and lead investigator on this study.

‘By examining gene expression data, we determined that the combination of the leukemia drug dasatinib (Sprycel®) made carboplatin and paclitaxel more effective in cell lines with higher levels of SRC expression and SRC pathway deregulation.’

That synergistic effect, in which drugs used in combination strengthen each other’s efficacy, was absent when low SRC expression and low SRC pathway deregulation were present, Teoh said.

‘These findings indicate that we may be able to direct the use of a targeted therapy like dasatinib based on gene expression pathways in select ovarian cancers,’ she said.

The results of the study are being presented on a poster at the 100th annual American Association for Cancer Research meeting in Denver on April 19, 2009. The study was funded by the Prudent Fund and the National Institutes of Health.

‘Our ultimate goal is to offer personalized therapy for women with ovarian cancer,’ said Angeles Secord, MD, a gynecologic oncologist at Duke and senior investigator on this study.

‘Hopefully in the future we will apply targeted therapies to individual patients and their cancers in order to augment response to treatment while minimizing toxic side effects.’

For this study, researchers examined four ovarian cancer cell lines, known as IGROV1, SKOV3, OVCAR3 and A2780. Three of the cell lines demonstrated high activation of SRC and one demonstrated lower SRC expression.

All were treated in lab dishes with various combinations of the chemotherapeutic agents dasatinib, carboplatin and paclitaxel.

‘We found that the addition of dasatinib to standard therapy in the three cell lines with significant SRC pathway deregulation – IGROV1, OVCAR3 and A2780 – enhanced the response of the cancer cells to therapy,’ Teoh said.

‘Conversely, in SKOV3, which has minimal SRC protein expression and pathway deregulation, we saw the least amount of anti-cancer activity when we added dasatinib.’

It’s possible that by blocking the SRC activity with the dasatinib, we are enhancing the effect of the other chemotherapeutic agents, Teoh said.

The results of this study support the further investigation of targeted biologic therapy using a SRC inhibitor in some ovarian cancers, she said. Currently a phase I trial of a combination of dasatinib, paclitaxel and carboplatin is available for women with advanced or recurrent ovarian, tubal and peritoneal cancers.

Dasatinib is a chemotherapeutic that is currently FDA-approved for use in leukemia. It is manufactured by Bristol-Myers Squibb and is sold under the brand name Sprycel. Bristol-Myers Squibb provided the dasatinib used in this study.

Other researchers involved in this study include Tina Ayeni, Jennifer Rubatt, Regina Whitaker, Holly Dressman and Andrew Berchuck.”

Source: Addition of Dasatinib to Standard Chemo Cocktail May Enhance Effect in Certain Ovarian Cancer, by Duke Medicine News and Communications, News, Health Library, DukeHealth.org, April 13, 2009.

Secondary Sources:

• Teoh D, Ayeni TA, Rubatt JM, Whitaker RS, Dressman HK, Berchuck A, Secord AA. In vitro characterization of the antitumor effects of dasatinib (BMS-354825) in combination with paclitaxel and carboplatin in human ovarian cancer cell lines . In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract #828.

• A Phase I Trial of A SRC Kinase Inhibitor, Dasatinib,in Combination With Paclitaxel and Carboplatin in Patients With Advanced or Recurrent Ovarian, Peritoneal, and Tubal Cancer, Clinical Trial Summary, National Institutes of Health, http://www.ClinicalTrials.gov.

Tumor-Promoting Protein COX-2 Is The Target Of First Joint Symposium Between AACR & ASCO

“An inflammatory protein implicated in a variety of cancers is the target of the first joint symposium between the nation’s two premier cancer research organizations.  The presidents of the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) organized the session focused on the COX-2 enzyme and cancer treatment Monday afternoon — April 20, 2:30-4:30 p.m., in rooms 205-207 of the Colorado Convention Center — at the AACR’s 100th Annual Meeting 2009 in Denver.  A similar symposium on new molecular targets will be conducted at ASCO’s annual meeting in May 29- June 2 in Orlando.  COX-2 is best known as a target for preventing dangerous polyps that lead to colorectal cancer, but it is also advancing as a target for treatment of many solid tumors. …“

“Leading cancer organizations team up on tumor-promoting protein – AACR and ASCO begin joint symposia at annual meetings with focus on COX-2

An inflammatory protein implicated in a variety of cancers is the target of the first joint symposium between the nation’s two premier cancer research organizations.

Raymond DuBois, M.D., Ph.D., President, AACR; Provost and Executive Vice President, The University of Texas M. D. Anderson Cancer Center

The presidents of the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) organized the session focused on the COX-2 enzyme and cancer treatment Monday afternoon — April 20, 2:30-4:30 p.m., in rooms 205-207 of the Colorado Convention Center — at the AACR’s 100th Annual Meeting 2009 in Denver. A similar symposium on new molecular targets will be conducted at ASCO’s annual meeting in May 29- June 2 in Orlando.

COX-2 is best known as a target for preventing dangerous polyps that lead to colorectal cancer, but it is also advancing as a target for treatment of many solid tumors.

‘Our symposium is timely because we are starting to see data from Phase II and Phase III clinical trials about COX-2 inhibition following post-surgical chemotherapy in colon cancer patients,’ said Raymond DuBois, M.D., Ph.D., president of AACR and provost and executive vice president at The University of Texas M. D. Anderson Cancer Center.

‘There’s been a great deal of preclinical and translational research addressing COX-2 overexpression in tumors and its role in cancer growth and survival. In prevention, inhibiting this enzyme reduces the number of high-risk precancerous polyps by 66 percent,’ DuBois said. ‘The time is ripe to combine basic science and clinical expertise to advance the therapeutic potential of this approach.’

Joint efforts are critical to the development of new approaches against cancer, said ASCO President Richard L. Schilsky, M.D., professor of medicine at the University of Chicago Medical Center.

‘The development of targeted therapies for cancer prevention and treatment requires the close collaboration and combined resources of basic scientists and clinical investigators,’ Schilsky said. ‘The success of targeted therapy for cancer depends first and foremost on a comprehensive understanding of the biology of the drug target coupled with a robust assay to assess target inhibition and a drug that hits the target. With these ingredients in place, clinical trials can be designed to assess the impact of treatment in the population most likely to benefit.’

Richard L. Schilsky, M.D., President, ASCO; Associate Dean for Clinical Research, Professor of Medicine at the University of Chicago Medical Center.

‘The AACR/ASCO Symposium illustrates these core principles and demonstrates that continued progress against cancer requires the partnership of all investigators and practitioners represented by these two great organizations,’ Schilsky said.

The idea for joint symposia at each organization’s annual meeting has been discussed for years and was advanced by immediate past presidents William Hait, M.D., Ph.D., of AACR and Nancy Davidson, M.D., of ASCO.

DuBois and Schilsky co-chair the symposium. Scheduled presentations are:

• COX-2 and Cancer Biology by DuBois, who discovered the enzyme’s overexpression in tumors.

• Overview of COX-2 as a Target for Cancer Treatment, by Schilsky.

• COX-2 in Lung Cancer: Rebirth as a Target, by Martin Edelman, M.D., of the University of Maryland.

• COX-2 as a Target for Prevention and Treatment of Colorectal Cancer by Andrew Chan, M.D., of Massachusetts General Hospital.

• Early Epigenetic and Genetic Events in Carcinogenesis by Thea D. Tlsty, Ph.D., of the University of California School of Medicine, San Francisco.

• A Mouse Model for COX-2 Driven Pancreatitis and Pancreatic Ductal Carcinoma by Susan Fischer, Ph.D. of M. D. Anderson Cancer Center Science Park – Research Division, Smithville, Texas.”

*          *          *

AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. ASCO is the world’s leading professional organization representing physicians who care for people with cancer. Many scientists and physicians are members of both organizations.”

Source: Leading Cancer Organizations Team Up on Tumor-Promoting Protein – AACR and ASCO begin joint symposia at annual meetings with focus on COX-2, M.D. Anderson News Release, The University of Texas M.D. Anderson Cancer Center, April 17, 2009.

Comment:  The relationship between ovarian cancer and COX-2 remains unclear.  Some in vitro and in vivo studies make a connection between ovarian cancer and COX-2, while others suggest that COX-1 is more relevant to current ovarian cancer research.  It is an area that warrants further investigation.

Recent Studies Re Ovarian Cancer and COX-2:

• Gu P, Su Y, Guo S, Teng L, Xu Y, Qi J, Gong H, Cai Y. Over-expression of COX-2 induces human ovarian cancer cells (CAOV-3) viability, migration and proliferation in association with PI3-k/Akt activation. Cancer Invest. 2008 Oct;26(8):822-9. PubMed PMID: 18798061.

• Li W, Zhang HH, Xu RJ, Zhuo GC, Hu YQ, Li J. Effects of a selective cyclooxygenase-2 inhibitor, nimesulide, on the growth of ovarian carcinoma in vivo. Med Oncol. 2008;25(2):172-7. Epub 2007 Oct 6. PubMed PMID: 18488158.

• Athanassiadou P, Grapsa D, Athanassiades P, Gonidi M, Athanassiadou AM, Tsipis A, Patsouris E. The prognostic significance of COX-2 and survivin expression in ovarian cancer. Pathol Res Pract. 2008;204(4):241-9. Epub 2008 Jan 2. PubMed PMID: 18171606.

• European Cancer Conference. Mutation Of The COX2 Gene Can Double Or Triple A Woman’s Risk Of Ovarian Cancer. ScienceDaily 27 September 2007. 19 April 2009 <http://www.sciencedaily.com­ /releases/2007/09/070925095320.htm>.

• Xin B, Yokoyama Y, Shigeto T, Futagami M, Mizunuma H. Inhibitory effect of meloxicam, a selective cyclooxygenase-2 inhibitor, and ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, on the growth of human ovarian cancers. Cancer. 2007 Aug 15;110(4):791-800. PubMed PMID: 17582802.

• Cao DY, Shen K, Yang JX, Guan J. [The expression of MRP, GST-pi, Topo IIalpha and COX-2 in epithelial ovarian cancer and its relationship to drug resistance and prognosis]. Zhonghua Yi Xue Za Zhi. 2007 Jul 3;87(25):1738-41. Chinese. PubMed PMID: 17919376.

• Barnes AP, Miller BE, Kucera GL. Cyclooxygenase inhibition and hyperthermia for the potentiation of the cytotoxic response in ovarian cancer cells. Gynecol Oncol. 2007 Feb;104(2):443-50. Epub 2006 Sep 22. PubMed PMID: 16996114.

• Xin B, Yokoyama Y, Shigeto T, Mizunuma H. Anti-tumor effect of non-steroidal anti-inflammatory drugs on human ovarian cancers. Pathol Oncol Res. 2007;13(4):365-9. Epub 2007 Dec 25. PubMed PMID: 18158574.

• Niesporek S, Weichert W, Sinn B, Röske A, Noske A, Buckendahl AC, Wirtz R, Sehouli J, Koensgen D, Dietel M, Denkert C. [NF-kappaB subunit p65/RelA expression in ovarian carcinoma: prognostic impact and link to COX-2 overexpression]. Verh Dtsch Ges Pathol. 2007;91:243-9. German. PubMed PMID: 18314621.

• Wang HJ, Liu XJ, Yang KX, Luo FM, Lou JY, Peng ZL. [Effects of nonsteroidal anti-inflammatory drug celecoxib on expression of cyclooxygenase-2 (COX-2) in ovarian carcinoma cell]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Sep;37(5):757-60. Chinese. PubMed PMID: 17037745.

• Vital-Reyes V, Rodríguez-Burford C, Chhieng DC, Oelschlager DK, Reyes-Fuentes A, Barnes M, Grizzle WE. Celecoxib inhibits cellular growth, decreases Ki-67 expression and modifies apoptosis in ovarian cancer cell lines. Arch Med Res. 2006 Aug;37(6):689-95. PubMed PMID: 16824926.

• Ferrandina G, Ranelletti FO, Martinelli E, Paglia A, Zannoni GF, Scambia G. Cyclo-oxygenase-2 (Cox-2) expression and resistance to platinum versus platinum/paclitaxel containing chemotherapy in advanced ovarian cancer. BMC Cancer. 2006 Jul 11;6:182. PubMed PMID: 16831230; PubMed Central PMCID: PMC1534059.

• Daikoku T, Tranguch S, Trofimova IN, Dinulescu DM, Jacks T, Nikitin AY, Connolly DC, Dey SK. Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer. Cancer Res. 2006 Mar 1;66(5):2527-31. PubMed PMID: 16510568.

Senator Barbara Boxer Reintroduces Legislation to Better Diagnosis Ovarian Cancer

On March 31, 2009, U.S. Senator Barbara Boxer (D-CA) reintroduced the Ovarian Cancer Biomarker Research Act of 2009 (H.R. 1816) legislation to develop new technologies to detect and fight ovarian cancer.  The Ovarian Cancer Biomarker Research Act bill, if ultimately enacted as law, would authorize $30 million each year for four years to fund research and development of reliable screening techniques for ovarian cancer. The bill would also authorize clinical trials to verify research techniques and bring together a panel of experts to evaluate and direct the progress of the work.

Senator Barbara Boxer of the State of California

On March 31, 2009, U.S. Senator Barbara Boxer (D-CA) reintroduced the Ovarian Cancer Biomarker Research Act of 2009 (H.R. 1816) legislation to develop new technologies to detect and fight ovarian cancer.  The Ovarian Cancer Biomarker Research Act bill, if ultimately enacted as law, would authorize $30 million each year for four years to fund research and development of reliable screening techniques for ovarian cancer. The bill would also authorize clinical trials to verify research techniques and bring together a panel of experts to evaluate and direct the progress of the work.

Upon reintroduction of  H.R. 1816, Senator Boxer said, “Early detection is key to helping more women beat this dangerous disease. When ovarian cancer is diagnosed in its early stages, more than 93 percent of women go on to live longer than five years. I am proud to sponsor this bill that makes a commitment to fight ovarian cancer with every possible tool.”

Congressman Howard L. Berman (D-CA) also reintroduced the Ovarian Cancer Biomarker Research Act of 2009 on March 31st in the U.S. House of Representatives.

The complete text of H.R. 1816, the Ovarian Cancer Biomarker Research Act of 2009, is set forth below.  This is the original text of the bill as it was written by its sponsor and submitted to the U.S. House of Representatives for consideration.  For an Adobe Reader PDF copy of H.R. 1816, CLICK HERE.

This bill is in the first step in the U.S. legislative process. Introduced bills and resolutions first go to committees that deliberate, investigate, and revise them before they go to general debate. The majority of bills and resolutions never make it out of committee.  Contact your U.S. Representative and let him or her know that you support this bill.

Source: Boxer Reintroduces Legislation to Better Diagnose Ovarian Cancer, Press Release, Office of Senator Barbara Boxer, April 1, 2009.

_____________________________________________

HR 1816:  Ovarian Cancer Biomarker Research Act of 2009

111th CONGRESS

1st Session

H. R. 1816

To amend the Public Health Service Act to authorize the Director of the National Cancer Institute to make grants for the discovery and validation of biomarkers for use in risk stratification for, and the early detection and screening of, ovarian cancer.

IN THE HOUSE OF REPRESENTATIVES

March 31, 2009

Mr. BERMAN (for himself, Mr. HALL of Texas, Ms. BORDALLO, Ms. LEE of California, Mr. VAN HOLLEN, Mr. MCGOVERN, Mr. MCDERMOTT, Mr. BOUCHER, Mr. KING of New York, Mr. GENE GREEN of Texas, Mr. WOLF, Ms. KILROY, Mr. BURTON of Indiana, Mr. ISRAEL, Mr. HINCHEY, Mr. SESTAK, Ms. DELAURO, Ms. SHEA-PORTER, Mrs. MALONEY, Mr. MCMAHON, Ms. WASSERMAN SCHULTZ, Mrs. CAPPS, Mr. SERRANO, Mr. FARR, and Ms. EDWARDS of Maryland) introduced the following bill; which was referred to the Committee on Energy and Commerce

A BILL

To amend the Public Health Service Act to authorize the Director of the National Cancer Institute to make grants for the discovery and validation of biomarkers for use in risk stratification for, and the early detection and screening of, ovarian cancer.

Be it enacted by the Senate and House of Representatives of the United States of America in Congress assembled,

SECTION 1. SHORT TITLE.

This Act may be cited as the ‘Ovarian Cancer Biomarker Research Act of 2009′.

SEC. 2. GRANTS FOR ESTABLISHMENT AND OPERATION OF RESEARCH CENTERS FOR THE STUDY OF OVARIAN CANCER BIOMARKERS.

Subpart 1 of part C of the Public Health Service Act is amended by adding at the end the following new section:

‘SEC. 417G. GRANTS FOR ESTABLISHMENT AND OPERATION OF RESEARCH CENTERS FOR THE STUDY OF OVARIAN CANCER BIOMARKERS.

‘(a) In General- The Director of the Institute, in consultation with the directors of other relevant institutes and centers of the National Institutes of Health and the Department of Defense Ovarian Cancer Research Program, shall enter into cooperative agreements with, or make grants to, public or nonprofit entities to establish and operate centers to conduct research on biomarkers for use in risk stratification for, and the early detection and screening of, ovarian cancer, including fallopian tube cancer or primary peritoneal cancer. Each center shall be known as an Ovarian Cancer Biomarker Center of Excellence, and shall focus on translational research of ovarian cancer biomarkers.

‘(b) Research Funded- Federal payments made under a cooperative agreement or grant under subsection (a) may be used for research on any of the following:

‘(1) The development and characterization of new biomarkers, and the refinement of existing biomarkers, for ovarian cancer.

‘(2) The clinical and laboratory validation of such biomarkers, including technical development, standardization of assay methods, sample preparation, reagents, reproducibility, portability, and other refinements.

‘(3) The development and implementation of clinical and epidemiological research on the utilization of biomarkers for the early detection and screening of ovarian cancer.

‘(4) The development and implementation of repositories for new tissue, urine, serum, and other biological specimens (such as ascites and pleural fluids).

‘(5) Genetics, proteomics, and pathways of ovarian cancer as they relate to the discovery and development of biomarkers.

‘(c) First Agreement or Grant- Not later than 1 year after the date of the enactment of this section, the Director of the Institute shall enter into the first cooperative agreement or make the first grant under this section.

‘(d) Availability of Banked Specimens- The Director of the Institute shall make available for research conducted under this section banked serum and tissue specimens from clinical research regarding ovarian cancer that was funded by the Department of Health and Human Services.

‘(e) Report- Not later than the end of fiscal year 2010, and annually thereafter, the Director of the Institute shall submit a report to the Congress on the cooperative agreements entered into and the grants made under this section.

‘(f) Authorization of Appropriations- For the purpose of carrying out this section, there are authorized to be appropriated $25,000,000 for each of the fiscal years 2010 through 2013, and such sums as may be necessary for each of the fiscal years 2014 through 2020. Such authorization of appropriations is in addition to any other authorization of appropriations that is available for such purpose.’.

SEC. 3. OVARIAN CANCER BIOMARKER CLINICAL TRIAL COMMITTEE.

Subpart 1 of part C of the Public Health Service Act, as amended by section 2, is further amended by adding at the end the following new section:

‘SEC. 417H. OVARIAN CANCER BIOMARKER CLINICAL TRIAL COMMITTEE.

‘(a) Ovarian Cancer Biomarker Research Committee Established- The Director of the Institute shall establish an Ovarian Cancer Biomarker Clinical Trial Committee (in this section referred to as the ‘Committee’) to assist the Director to design and implement one or more national clinical trials, in accordance with this section, to determine the utility of using biomarkers validated pursuant to the research conducted under section 417E for risk stratification for, and early detection and screening of, ovarian cancer.

‘(b) Membership-

‘(1) NUMBER- The Committee shall consist of 11 voting members and such number of nonvoting members as the Director of the Institute determines appropriate.

‘(2) APPOINTMENT- The members of the Committee shall be appointed by the Director of the Institute, in consultation with appropriate national medical societies, research societies, and patient advocate organizations, as follows:

‘(A) VOTING MEMBERS- The voting members of the Committee shall be appointed by the Director of the Institute as follows:

‘(i) Two patient advocates.

‘(ii) Two national experts in statistical analysis, clinical trial design, and patient recruitment.

‘(iii) Two representatives from the Gynecologic Oncology Group.

‘(iv) One representative from the Department of Defense Ovarian Cancer Research Program.

‘(v) Four ovarian cancer researchers.

‘(B) NONVOTING MEMBERS- The nonvoting members of the Committee shall include such individuals as the Director of the Institute determines to be appropriate.

‘(3) PAY- Members of the Committee shall serve without pay and those members who are full time officers or employees of the United States shall receive no additional pay by reason of their service on the Committee, except that members of the Committee shall receive travel expenses, including per diem in lieu of subsistence, in accordance with applicable provisions under chapter I of chapter 57 of title 5, United States Code.

‘(c) Chairperson- The voting members of the Committee appointed under subsection (b)(2) shall select a chairperson from among such members.

‘(d) Meetings- The Committee shall meet at the call of the chairperson or upon the request of the Director of the Institute, but at least four times each year.

‘(e) Clinical Trial Specifications- In designing and implementing the clinical trials under this section, the Director of the Institute shall provide for the following:

‘(1) PARTICIPATION IN TRIAL- To the greatest extent possible, all academic centers, community cancer centers, and individual physician investigators (as defined in subsection (f)) shall have the opportunity to participate in the trials under this section and to enroll women at risk for ovarian cancer in the trials.

‘(2) COSTS FOR ENROLLMENTS- Subject to the availability of appropriations, all the costs to the centers and offices described in paragraph (1) for enrolling women in the trials under this section shall be reimbursed by the Institute.

‘(3) NATIONAL DATA CENTER- A national data center shall be established in and supported by the Institute to conduct statistical analyses of the data derived from the trials under this section and to store such analyses and data.

‘(4) GUIDELINES FOR MEDICAL COMMUNITY- Data and statistical analyses of the clinical trials under this section shall be used to establish clinical guidelines to provide the medical community with information regarding the use of biomarkers validated pursuant to the research conducted under section 417E for risk stratification for, and early detection and screening of, ovarian cancer.

‘(f) Individual Physician Investigator Defined- For purposes of subsection (e)(1), the term ‘individual physician investigator’ means a physician–

‘(1) who is a faculty member at an academic institution or who is in a private medical practice; and

‘(2) who provides health care services to women at risk for ovarian cancer.

‘(g) Report- Not later than the end of fiscal year 2010, and annually thereafter, the Director of the Institute shall submit a report to the Congress on the activities conducted under this section.

‘(h) Authorization of Appropriations- For the purpose of carrying out this section, there are authorized to be appropriated $5,000,000 for each of the fiscal years 2010 through 2013, and such sums as may be necessary for each of the fiscal years 2014 through 2020. Such authorization of appropriations is in addition to any other authorization of appropriations that is available for such purpose.’.

Stanford Researchers Harness Nanoparticles To Track Cancer Cell Changes

“A new imaging technology could give scientists the ability to simultaneously measure as many as 100 or more distinct features in or on a single cell. In a disease such as cancer, that capability would provide a much better picture of what’s going on in individual tumor cells. A Stanford University School of Medicine team led by Cathy Shachaf, PhD, an instructor in microbiology and immunology, has for the first time used specially designed dye-containing nanoparticles to simultaneously image two features within single cells. … In a study published April 15 in the online journal PLoS-ONE, the Stanford team was able to simultaneously monitor changes in two intracellular proteins that play crucial roles in the development of cancer. Successful development of the new technique may improve scientists’ ability not only to diagnose cancers-for example, by determining how aggressive tumors’ constituent cells are-but to eventually separate living, biopsied cancer cells from one another based on characteristics indicating their stage of progression or their degree of resistance to chemotherapeutic drugs….”

“STANFORD, Calif. – The more dots there are, the more accurate a picture you get when you connect them. A new imaging technology could give scientists the ability to simultaneously measure as many as 100 or more distinct features in or on a single cell. In a disease such as cancer, that capability would provide a much better picture of what’s going on in individual tumor cells.

Catherine Shachaf, Instructor, Microbiology & Immunology - Baxter Laboratory, Stanford School of Medicine

A Stanford University School of Medicine team led by Cathy Shachaf, PhD, an instructor in microbiology and immunology, has for the first time used specially designed dye-containing nanoparticles to simultaneously image two features within single cells. Although current single-cell flow cytometry technologies can do up to 17 simultaneous visualizations, this new method has the potential to do far more. The new technology works by enhancing the detection of ultra-specific but very weak patterns, known as Raman signals, that molecules emit in response to light.

In a study published April 15 in the online journal PLoS-ONE, the Stanford team was able to simultaneously monitor changes in two intracellular proteins that play crucial roles in the development of cancer. Successful development of the new technique may improve scientists’ ability not only to diagnose cancers-for example, by determining how aggressive tumors’ constituent cells are-but to eventually separate living, biopsied cancer cells from one another based on characteristics indicating their stage of progression or their degree of resistance to chemotherapeutic drugs. That would expedite the testing of treatments targeting a tumor’s most recalcitrant cells, said Shachaf, a cancer researcher who works in a laboratory run by the study’s senior author, Garry Nolan, PhD, associate professor of microbiology and immunology and a member of Stanford’s Cancer Center.

Cancer starts out in a single cell, and its development is often heralded by changes in the activation levels of certain proteins. In the world of cell biology, one common way for proteins to get activated is through a process called phosphorylation that slightly changes a protein’s shape, in effect turning it on.

Two intracellular proteins, Stat1 and Stat6, play crucial roles in the development of cancer. The Stanford team was able to simultaneously monitor changes in phosphorylation levels of both proteins in lab-cultured myeloid leukemia cells. The changes in Stat1 and Stat6 closely tracked those demonstrated with existing visualization methods, establishing proof of principle for the new approach.

While the new technology so far has been used only to view cells on slides, it could eventually be used in a manner similar to flow cytometry, the current state-of-the-art technology, which lets scientists visualize single cells in motion. In flow cytometry, cells are bombarded with laser light as they pass through a scanning chamber. The cells can then be analyzed and, based on their characteristics, sorted and routed to different destinations within the cytometer.

Garry Nolan, Associate Professor, Microbiology & Immunology - Baxter Laboratory; Member, Bio-X; Member, Stanford Cancer Center, Stanford School of Medicine

Still, flow cytometry has its limits. It involves tethering fluorescent dye molecules to antibodies, with different colors tied to antibodies that target different molecules. The dye molecules respond to laser light by fluorescing-echoing light at exactly the same wavelength, or color, with which they were stimulated. The fluorescence’s strength indicates the abundance of the cell-surface features to which those dyes are now attached. But at some point, the light signals given off by multiple dyes begin to interfere with one another. It is unlikely that the number of distinct features flow cytometry can measure simultaneously will exceed 20 or so.

The new high-tech dye-containing particles used by the Stanford team go a step further. They give off not just single-wavelength fluorescent echoes but also more-complex fingerprints comprising wavelengths slightly different from the single-color beams that lasers emit. These patterns, or Raman signals, occur when energy levels of electrons are just barely modified by weak interactions among the constituent atoms in the molecule being inspected.

Raman signals are emitted all the time by various molecules, but they’re ordinarily too weak to detect. To beef up their strength, the Stanford team employed specialized nanoparticles produced by Intel Corp., each with its own distinctive signature. Intel has designed more than 100 different so-called COINs, or composite organic–inorganic nanoparticles: These are essentially sandwiches of dye molecules and atoms of metals such as silver, gold or copper whose reflective properties amplify a dye molecule’s Raman signals while filtering out its inherent fluorescent response. The signals are collected and quantified by a customized, automated microscope.

Shachaf anticipates being able to demonstrate simultaneous visualization of nine or 10 COIN-tagged cellular features in the near future and hopes to bring that number to 20 or 30, a new high, before long. ‘The technology’s capacity may ultimately far exceed that number,’ she added. Some day it could be used for more than 100 features. Meanwhile, another group outside Stanford, now collaborating with the Nolan group, has developed a prototype device that can detect Raman signals in a continuous flow of single cells, analogous to flow cytometry but with higher resolving power, Shachaf said.

The study was funded by the National Cancer Institute’s Center for Cancer Nanotechnology Excellence Focused on Therapy Response and by the Flight Attendant Medical Research Institute. Other Stanford contributors were researchers Sailaja Elchuri, PhD, and Dennis Mitchell of the Nolan lab; engineering and materials science graduate student Ai Leen Koh; and Robert Sinclair, PhD, professor of materials science and engineering.

# # #

The Stanford University School of Medicine consistently ranks among the nation’s top 10 medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children’s Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.”

Source: Stanford researchers harness nanoparticles to track cancer cell changes, by Bruce Goldman, News Release, Stanford School of Medicine, April 14, 2009.

Primary Citation:  Shachaf CM, Elchuri SV, Koh AL, Zhu J, Nguyen LN, et al. 2009  A Novel Method for Detection of Phosphorylation in Single Cells by Surface Enhanced Raman Scattering (SERS) using Composite Organic-Inorganic Nanoparticles (COINs). PLoS ONE 4(4): e5206. doi:10.1371/journal.pone.000520. For an Adobe Reader PDF copy of the study, CLICK HERE.

FDA Grants Paclical “Orphan Drug” Designation

“Oasmia Pharmaceutical, Uppsala, Sweden, has been granted Orphan Drug designation by the USA FDA of Paclical® for the treatment of ovarian cancer. Orphan Drug designation can entail additional assistance from FDA to expedite and optimize drug development and upon approval a seven year market exclusivity is granted. …”

“Oasmia: FDA grants Paclical® Orphan Drug Designation for ovarian cancer in the USA

Julian Aleksov, CEO, Oasmia Pharmaceutical AB

Oasmia Pharmaceutical, Uppsala, Sweden, has been granted Orphan Drug designation by the USA FDA of Paclical® for the treatment of ovarian cancer. Orphan Drug designation can entail additional assistance from FDA to expedite and optimize drug development and upon approval a seven year market exclusivity is granted.

Orphan drug designation is intended to support the clinical development of new drugs in diseases affecting less than 200,000 people. This provides Oasmia with seven year market exclusivity on the indication when the pharmaceutical is approved. There is no direct generic competition during the period and FDA often provides technical and financial assistance to expedite and optimize drug development.

The designation is based on the hypothesis that Paclitaxel is safer than Taxol®. Oasmia Pharmaceutical is conducting a Phase III study comparing the use of Paclical to Taxol® in patients with ovarian cancer. A safety objective is to show the superiority of hypersensitivity reactions.

This designation shows that the FDA has a great confidence in the company and our product. The United States is one of the most important markets for Paclical®. This decision improves the possibilities for the product, says Julian Aleksov, CEO of Oasmia in a comment.

About Ovarian Cancer
Ovarian cancer is a disease with few and unspecific symptoms at its early stages, and is difficult to detect. The numbers of patients that are diagnosed are increasing on a yearly basis. Ovarian cancer is most often diagnosed in women over 50 years of age, but younger women are also affected. The annual incidence of new diagnosed cases is approximately 125,000 women in EU [European Union] alone. In the USA ovarian cancer accounts for 3 % of all cancer cases and is the fifth leading cause of cancer related deaths in the US.

About Paclical®
With the retinoid based unique platform XR-17, Oasmia has managed to produce a water soluble formulation of Paclitaxel (Paclical®), that does not require premedication and without the severe Cremophor® EL related side effects. The main indication is ovarian cancer. Other planned indications are malignant melanoma and lung cancer (NSCLC).

About Oasmia
Oasmia Pharmaceutical AB develops second and third generation cancer drugs based on nanotechnology for human and veterinary use. The broad portfolio is focused on oncology and contains several promising products in clinical and pre-clinical phase. Oasmia cooperates with leading universities and other biotech companies to discover and optimize substances with a favourable safety profile and better efficacy. The company was founded in 1998 and is based in Uppsala, Sweden. …”

Source: Oasmia: FDA grants Paclical® Orphan Drug Designation for ovarian cancer in the USA, Oasmia Pharmaceutical AB, April 14, 2009.

CNTO 328 Shows Promise For Ovarian Cancer In Small Clinical Trial, Say U.K. Scientists.

British scientists have developed and clinically tested a drug that could prolong the lives of ovarian cancer patients. A clinical trial of the drug, codenamed CNTO328, has been carried out at the Centre for Experimental Cancer Medicine, which is part of Barts and the London School of Medicine and Dentistry. … The drug is an antibody which works by targeting a molecule called Interleukin 6, which is made by cancer cells and is vital to help them multiply, spread and develop their own blood supply. … “At the end of the trial, eight of the women were either stable or getting better. Their cancer had stopped growing. That doesn’t sound great, but in ovarian cancer that’s pretty good because [without the drug] the disease would have progressed in all of them,” said McNeish.

British scientists have developed and clinically tested a drug that could prolong the lives of ovarian cancer patients.  A clinical trial of the drug, codenamed CNTO328, has been carried out at the Centre for Experimental Cancer Medicine, which is part of Barts and the London School of Medicine and Dentistry.

Eight of the 18 women enrolled in the trial experienced tumor stabilization or shrinkage.  The investigators noted that the percentage of women who received clinical benefit from CNTO328 is an unusually high proportion for an experimental cancer drug study. Typically only between 5%  and 20% of participants secure any benefit from taking untried treatments, according to the investigators.

Iain McNeish, MA, Ph.D., MRCP, Professor of Gynecological Oncology, Honorary Consultant in Medical Oncology, Deputy Director Centre for Experimental Cancer Medicine Centre for Molecular Oncology & Imaging, Barts and the London School of Medicine & Denistry, London, United Kingdom

Professor Iain McNeish, a professor of gynaecological oncology at Barts hospital in London and chief investigator of the trial, said: “We have taken the drug from the laboratory into patients and the results are promising.  The hope with this group of patients was to slow down the progress of their ovarian cancer, improve the quality of their life and possibly make them live longer. We have been quite successful in doing that. If this becomes a treatment, this is a whole new approach to treating ovarian cancer.”

The drug is an antibody which works by targeting a molecule called Interleukin 6, which is made by cancer cells and is vital to help them multiply, spread and develop their own blood supply.  Interleukin 6 is found in many cancers but plays a key role in ovarian cancer’s movement into the abdomen. The antibody binds to the Interleukin 6, blocks its progress by ensuring that it cannot bind itself to the cancer cells to assist their growth and thus renders it harmless.

McNeish hopes that, if further trials confirm the drug’s potential, it could prove as effective in tackling ovarian cancer as Herceptin has been in breast cancer. CNTO328 works in a similar way to Herceptin, which has revolutionized breast cancer treatment in recent years. “The dream scenario is that a combination of the existing chemotherapy drugs and this type of antibody will be a big breakthrough and open up a new avenue for the treatment of ovarian cancer”, said McNeish.

The new drug is the result of a collaboration between Professor Fran Balkwill, an expert in cancer and inflammation at the Institute of Cancer, Barts and the London School of Medicine and Denistry, and a Dutch biotech company called Centocor, which is now owned by Johnson & Johnson.

Eighteen women with the disease from north-east London and Essex joined the trial which began in late 2007.  All 18 were expected to live for less than a year when they began receiving the drug because their cancer had returned after undergoing several courses of chemotherapy.  Ten women died but the health of eight women improved. Seven of those eight women are still alive.  “At the end of the trial, eight of the women were either stable or getting better. Their cancer had stopped growing. That doesn’t sound great, but in ovarian cancer that’s pretty good because [without the drug] the disease would have progressed in all of them,” said McNeish.

Annwen Jones, chief executive of the UK charity Target Ovarian Cancer, said there were too few drugs available to treat ovarian cancer because of a lack of research. “This early stage trial certainly shows promise, because it appears that the growth of tumors has been slowed down in a good proportion of the patients who took part in the study,” said Jones. “Women being treated for ovarian cancer could be forgiven for despair, particularly when they grow resistant to chemotherapy and there are no drugs that can get them over this hurdle. Research projects like this are vital if we are to develop desperately needed new treatments,” she said.

Primary Sources:

• New drug ‘could prolong life of ovarian cancer sufferers’- A drug that could prolong the lives of women with ovarian cancer is being tested by scientists, Health News, Telegraph.co.uk., April 7, 2009.

• Ovarian cancer breakthrough – Drug could be available within five years – First new treatment in a decade is by British team, by Denis Campbell, Health Correspondent, Health section, The Hindu, April 7, 2009.

Additional Resources:

• A Phase 1/2, Multiple-Dose, Dose-Escalation Study to Assess the Safety, Efficacy, and Pharmacokinetics of Intravenous CNTO 328, an Anti-Interleukin 6 (IL-6) Monoclonal Antibody, in Subjects With Solid Tumors, Clinical Trial Protocol (NCT00841191), National Institute of Health, http://www.ClinicalTrials.gov.

• CNTO328 Developer, Centocor Ortho Biotech Inc.

GOG Reports on Evaluation of Pemetrexed in Treatment of Recurrent Platinum-Resistant Ovarian Cancer

A phase II Gynecologic Oncology Group (GOG) clinical study found that pemetrexed (Altima®)-an antifolate antineoplastic agent that disrupts folate-dependent cell replication metabolic processes-is sufficiently active in the treatment of recurrent platinum-resistant ovarian cancer to warrant further investigation.  “Thus [pemetrexed] should be considered for combination with other agents, especially carboplatin, in first-line therapy,” said David Miller, M.D., F.A.C.S. (University of Texas Southwestern Medical Center, Dallas, USA) and colleagues.

David Miller, M.D. F.A.C.S., Professor, Gynecologic Oncology, University of Texas Southwestern Medical Center

A phase II Gynecologic Oncology Group (GOG) clinical study found that pemetrexed (Altima®)-an antifolate antineoplastic agent that disrupts folate-dependent cell replication metabolic processes-is sufficiently active in the treatment of recurrent platinum-resistant ovarian cancer to warrant further investigation.  “Thus [pemetrexed] should be considered for combination with other agents, especially carboplatin, in first-line therapy,” said David Miller, M.D., F.A.C.S. (University of Texas Southwestern Medical Center, Dallas, USA) and colleagues.

The purpose of the GOG study was to estimate the antitumor activity of pemetrexed in patients with persistent or recurrent, platinum-resistant epithelial ovarian or primary peritoneal cancer and to determine the nature and degree of toxicities.  The patients that participated in the study experienced disease progression on platinum-based primary chemotherapy or recurred within 6 months. Pemetrexed at a dose of 900 mg/m2 was administered as an intravenous infusion over 10 minutes every 21 days. Dose delay and adjustments were permitted for toxicity. Treatment was continued until disease progression or unacceptable adverse effects.  From July 6, 2004, to August 23, 2006, 51 patients enrolled in the study.  A total of 259 cycles (median, four; range one to 19 cycles) of pemetrexed were administered, with 40% of the patients receiving six or more cycles.

According to the investigators, the study produced the following results:

• Treatment was well tolerated, but grade 3 & 4 patient toxicities included neutropenia (42%), leukopenia (25%), anemia (15%), and constitutional (15%);

• No treatment -related deaths were reported;

• Eighteen patients (38%) had progressive disease. Three patients (6%) were not assessable;

• One patient (2%) had a complete response (CR) and nine patients (19%) had partial responses (PRs), with a median duration response of 8.4 months. Seventeen patients (35%) had stable disease (SD) for a median of 4.1 months. Clinical benefit rate (CR + PR + SD) was 56%; and

• Median progression-free survival was 2.9 months, and overall survival was 11.4 months.

Based upon the foregoing results, the investigators noted that pemetrexed “exhibited activity more favorable than that seen in other agents that have been test in first-line combinations by the GOG.” Pemetrexed, according to the investigators, has sufficient activity in the treatment of recurrent platinum-resistant ovarian cancer at the dose and schedule tested to warrant further investigation.

Sources:

• Miller DS, Blessing JA, Krasner CN et. al. Phase II Evaluation of Pemetrexed in the Treatment of Recurrent or Persistent Platinum-Resistant Ovarian or Primary Peritoneal Carcinoma: A Study of the Gynecologic Oncology Group. J. Clin. Onc., Early Release, published online ahead of print Mar. 30 2009, 10.1200/JCO.2008.19.2963.

• Pemetrexed effective treatment for recurrent platinum-resistant ovarian cancer, by Ingrid Grasmo, Medwire News, April 6, 2009.

Medicare Expands Coverage of PET Scans as Cancer Diagnostic Tool

“The Centers for Medicare & Medicaid Services (CMS) issued a final national coverage determination (NCD) to expand coverage for initial testing with positron emission tomography (PET) for Medicare beneficiaries who are diagnosed with and treated for most solid tumor cancers.  This decision applies to PET scans used to support initial diagnosis and treatment for most types of solid tumor cancers. … It also expands coverage of PET scans for subsequent follow up testing in beneficiaries who have cervical or ovarian cancer … A minimally invasive diagnostic imaging procedure, PET uses a radioactive tracer to evaluate glucose metabolism in tumors and in normal tissue. …”

“For Immediate Release: Monday, April 06, 2009
Contact: CMS Office of Public Affairs
202-690-6145

MEDICARE EXPANDS COVERAGE OF PET SCANS AS CANCER DIAGNOSTIC TOOL

CMS’ Coverage with Evidence Development Project Shows PET Scans as “Reasonable and Necessary” for Initial Treatment Decisions of Most Solid Tumor Cancers

Centers For Medicare & Medicaid Services

The Centers for Medicare & Medicaid Services (CMS) issued a final national coverage determination (NCD) to expand coverage for initial testing with positron emission tomography (PET) for Medicare beneficiaries who are diagnosed with and treated for most solid tumor cancers.

This NCD removes a clinical study requirement for PET scan use in these patients.

Since 2005, Medicare coverage of PET scans for diagnosing some forms of cancer and guiding treatment has been tied to a requirement that providers collect clinical information about how the scans have affected doctors’ treatment decisions. This information was gathered through the National Oncologic PET Registry (NOPR) observational study. This decision removes the requirement to report data to the NOPR when the PET scan is used to support initial treatment (or diagnosis and “staging“) of most solid tumor cancers.

Medicare collects data from the NOPR under CMS’ Coverage with Evidence Development (CED) program. CED allows Medicare to develop evidence about how a medical technology is used in clinical practice so that Medicare can do the following:

(a) clarify the impact of these items and services on the health of Medicare beneficiaries;

(b) consider future changes in coverage for the technology; and

(c) generate clinical information that will improve the evidence base upon which providers base their recommendations to Medicare beneficiaries regarding the technology.

This decision is based, in part, on the information generated as a result of CMS’ 2005 decision to require NOPR reporting for many cancer PET scans. As a result of this evidence from NOPR, CMS reconsidered its 2005 coverage policy. This decision is the first time that CMS has reconsidered a coverage policy based on new evidence developed under the CED program.

‘This expansion in coverage for PET scans shows that the Coverage with Evidence Development program is a success,’ said CMS Acting Administrator Charlene Frizzera. ‘CED allowed us to cover an emerging technology, learn more about its usage in clinical practice, and adjust our coverage policies accordingly. Thanks to CED, Medicare beneficiaries have greater access to cutting edge medical technologies and treatments.’

Positron Emission Tomography (PET) equipment (Photo Source: RadiologyInfo.org)

This decision applies to PET scans used to support initial diagnosis and treatment for most types of solid tumor cancers. It also expands coverage of PET scans for subsequent follow up testing in beneficiaries who have cervical or ovarian cancer, or who are being treated for myeloma, a cancer that affects white blood cells. For these cancers, NOPR data collection will no longer be required. [Emphasis added by Libby’s H*O*P*E*™]

It is important to note that today’s decision still requires clinicians to report data to the NOPR when using PET scans to monitor the progress of treatment or remission of cancer in some cases. Although the evidence generated by the NOPR study helped CMS determine that PET scans are useful in helping guide treatment when cancer is first diagnosed, scientific evidence is not as strong in showing that PET scans are as useful in making subsequent treatment decisions for some types of cancer.

A minimally invasive diagnostic imaging procedure, PET uses a radioactive tracer to evaluate glucose metabolism in tumors and in normal tissue. The test may provide important clinical information to guide the initial treatment approach (e.g., diagnosis and “staging”) for many cancers.

This additional information may help physicians to distinguish benign from cancerous lesions and better determine the extent of a tumor’s growth or metastasis. PET scans have also been used in subsequent testing for cancer patients, e.g., to monitor cancer progression or remission after cancer treatment has begun.

More information about the types of cancer covered by this new policy is available in CMS’ final decision memorandum. …”

Source:  Medicare Expands Coverage of PET Scans As Cancer Diagnostic Tool – CMS’ Coverage with Evidence Development Project Shows PET Scans as “Reasonable and Necessary” for Initial Treatment Decisions of Most Solid Tumor Cancers, Centers for Medicare & Medicaid Services, Press Release, April 6, 2009.

Secondary Sources:

• Decision Memo for Positron Emission Tomography (FDG) for Solid Tumors (CAG-00181R), Centers For Medicare & Medicaid Services, April 3, 2009 (includes CMS decision summary and decision memo). [CLICK HERE for Adobe Reader PDF doc.].

• Appendix A:  Effect of Coverage Changes on Oncologic Uses of FDG PET, Decision Memo for Positron Emission Tomography (FDG) for Solid Tumors (CAG-00181R), Centers For Medicare & Medicaid Services, April 3, 2009.

• Appendix C:  Evidence Tables – Studies of PET for Oncology Indications, Decision Memo for Positron Emission Tomography (FDG) for Solid Tumors (CAG-00181R), Centers For Medicare & Medicaid Services, April 3, 2009. [Adobe Reader PDF doc.]

Comment:  The CMS Decision Memo involving the use of PET scans for solid tumors allows an ovarian cancer patient (who is a Medicare beneficiary) to obtain a PET scan for “initial treatment strategy” purposes.  “Initial Treatment Strategy” is generally defined by CMS as encompassing initial diagnosis or staging.  An ovarian cancer patient (who is a Medicare beneficiary) can also obtain a PET scan for “subsequent treatment strategy” purposes.  “Subsequent Treatment Strategy” is generally defined by CMS as encompassing “restaging” and “monitoring response to treatment when a change in treatment is anticipated.”