ASCO 2011: Genetic Biomarker Predicts Taxane Drug-Induced Neuropathy

A new study has identified the first genetic biomarkers for taxane-induced peripheral neuropathy, a potentially severe complication of taxane chemotherapy that affects nerves in about one-third of patients with cancer receiving such treatment.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

New study results involving a genetic marker which can predict taxane drug-induced neuropathy were highlighted today in the ASCO press briefing, as summarized below.

Genetic Biomarker Predicts Taxane-Induced Neuropathy

A new study has identified the first genetic biomarkers for taxane drug-induced peripheral neuropathy, a potentially severe complication of taxane chemotherapy that affects nerves in about one-third of patients with cancer receiving such treatment. The finding may eventually lead to a simple blood test to determine whether a patient is at high risk for neuropathy.

Bryan P. Schneider, M.D., Physician & Researcher, Indiana University Melvin & Bren Simon Cancer Center; Associate Director, Indiana Institute for Personalized Medicine

“If these findings can be replicated, this may allow physicians to know prior to recommending therapy whether the patient is at an inordinate risk for developing taxane-induced neuropathy,” said Bryan P. Schneider, M.D., lead author and a physician/researcher at the Indiana University Melvin and Bren Simon Cancer Center and Associate Director for the Indiana Institute for Personalized Medicine. “This may allow for better counseling, use of alternative drugs or schedules, or omission of taxanes in the appropriate settings. These genetic findings might also provide insight into the mechanism of this side effect and help develop drugs to prevent this toxicity altogether.”

Such damage to the nerves can cause pain and numbness and limit the dose of chemotherapy a patient can receive. While only a few factors seem to predict which patients are likely to get peripheral neuropathy, including a history of diabetes and advanced age, genetic variations may explain why some patients are more sensitive to taxane drugs.

The authors conducted a genome wide association study on 2,204 patients enrolled in an Eastern Cooperative Oncology Group breast cancer clinical trial (E5103) in which all patients received taxane-based chemotherapy, namely paclitaxel (Taxol). The study looked for variations in DNA (deoxyribonucleic acid) called single nucleotide polymorphisms, or SNPs (pronounced “snips”), by evaluating more than 1.2 million SNPs in each patient.  A SNP is a DNA sequence variation which occurs when a single nucleotide — A (adenine), T (thymine), C (cytosine), or G (guanine) — in the genome (or other shared sequence) differs between two individuals, or between paired chromosomes located within the nucleus of an individual’s cells.

With a median follow-up of 15 months, the study identified genetic subgroups that were markedly more likely to develop peripheral neuropathy.

Those who carried two normal nucleotides in the RWDD3 gene had a 27 percent chance of experiencing neuropathy; those who carried one normal nucleotide and one SNP had a 40 percent risk; and those who carried two SNPs had a 60 percent risk.

In contrast, those who carried two normal nucleotides in the TECTA gene had a 29 percent chance of experiencing neuropathy; those who carried one normal nucleotide and one SNP had a 32 percent risk; and those who carried two SNPs had a 57 percent risk.

The study also found that older patients and African Americans were much more likely to have peripheral neuropathy, and further analysis of SNPs in these groups is underway.

The authors plan to continue their work in additional trials to validate these findings and to determine whether a different type or schedule of taxane therapy would result in less neuropathy in the more susceptible genetic groups. The authors also are collaborating with neurobiologists to understand why these genetic variations might make the nerves more sensitive to these drugs.

____________________

Sources:

• ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine – Genetic Biomarker Predicts Taxane-Induced Neuropathy, Press Release, American Society of Clinical Oncology, May 18, 2011. [Adobe Reader PDF]

• Schneider BP, Li L, Miller K, et. al. Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103. J Clin Oncol 29: 2011 (suppl; abstr 1000)(2011 ASCO Annual Meeting).

Resources:

• Genetic Variations Identify Patients Sensitive to Nerve Damage from Chemotherapy, http://www.Cancer.net, May 18, 2011.

FDA Awards $1.6M Orphan Drug Grant for Clinical Phase II Development of EGEN-001 for Treatment of Ovarian Cancer

EGEN, Inc. announced that the Food and Drug Administration (FDA) awarded the company a four-year grant of $1.6 million to assist in the phase II clinical development of EGEN-001, the company’s lead product. EGEN-001 is under clinical development for the treatment of advanced recurrent ovarian cancer.

EGEN, Inc. announced that the Food and Drug Administration (FDA) awarded the company a four-year grant of $1.6 million to assist in the phase II clinical development of EGEN-001, the company’s lead product. EGEN-001 is under clinical development for the treatment of advanced recurrent ovarian cancer.[1]

EGEN, Inc. is developing gene-based biopharmaceuticals that rely on proprietary delivery technologies such as TheraPlas™ (illustrated above). In preclinical studies, the application of this approach produced anti-cancer activity in the treatment of disseminated abdominal cancers, solid tumors and metastatic cancers. (Photo: EGEN, Inc.)

EGEN-001 was developed as an interleukin-12 (IL‑12) gene therapy for the treatment of disseminated epithelial ovarian cancer. It is a low concentration formulation composed of a human IL-12 plasmid formulated with a proprietary PPC delivery system. EGEN-001 is designed for intraperitoneal (IP) administration. The subsequent IL-12 protein expression is associated with an increase in immune system activity, including T-lymphocyte and natural killer (NK) cell proliferation, and cytotoxic activation and secretion of interferon gamma (IFN-g), which in turn, leads to tumor inhibition. Additionally, IL-12 inhibits angiogenesis and formation of tumor vascularization.

EGEN has successfully completed two Phase I trials of EGEN-001 in ovarian cancer patients.  In the first study, EGEN-001 was administered as monotherapy in platinum-resistant ovarian cancer patients[2] and in the second study in combination with carboplatin/docetaxel chemotherapy in platinum-sensitive ovarian cancer patients.[3] In both studies, EGEN-001 treatment resulted in good safety, biological activity and encouraging efficacy.[4-5] EGEN-001 received Orphan Drug Status from the FDA in 2005, and its first $1 million FDA orphan grant in 2005.

“This is a significant milestone and accomplishment for the company,” commented Dr. Khursheed Anwer, President and Chief Science Officer of EGEN. “We are pleased to receive this FDA support, which has been very useful in the advancement of our novel EGEN-001 product in the clinic for the treatment of recurrent ovarian cancer. The product utilizes the Company’s proprietary TheraPlas® delivery technology and is composed of interleukin-12 (IL-12) gene formulation with a biocompatible delivery polymer. IL-12 is a potent cytokine which works by enhancing the body’s immune system against cancer and inhibiting tumor blood supply.”

About EGEN, Inc.

EGEN, Inc. (EGEN), with laboratories and headquarters in Huntsville, Alabama, is a privately held biopharmaceutical company focused on developing therapeutics for the treatment of human diseases including cancer. The Company specializes in the delivery of therapeutic nucleic acids (DNA and RNAi) and proteins aimed at specific disease targets. The Company has a significant intellectual property position in synthetic carriers, their combination with DNA, and their therapeutic applications. EGEN’s research pipeline products are aimed at treatment of various cancer indications. In addition, the Company has its TheraSilence® delivery technology aimed at delivery of therapeutic siRNA for the treatment of human diseases. EGEN collaborates with outside investigators, biotech organizations, and universities on various projects in these areas.

References:

1/ A Phase II Evaluation of Intraperitoneal EGEN-001 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer, Clinical Trial Summary, ClinicialTrials.gov (Identifier:  NCT01118052).

2/A Phase 1, Open Label, Dose Escalation Study of the Safety, Tolerability and Preliminary Efficacy of Intraperitoneal EGEN-001 in Patients With Recurrent Epithelial Ovarian Cancer, Clinical Trial Summary, ClinicialTrials.gov (Identifier: NCT00137865).

3/A Phase 1, Open-Label, Dose Escalation Study of the Safety and Preliminary Efficacy of EGEN-001 in Combination With Carboplatin and Docetaxel in Women With Recurrent, Platinum-Sensitive, Epithelial Ovarian Cancer, Clinical Trial Summary, ClinicialTrials.gov (Identifier:  NCT00473954).

4/Kendrick JE, Matthews KS, Straughn JM, et. al.  A phase I trial of intraperitoneal EGEN-001, a novel IL-12 gene therapeutic, administered alone or in combination with chemotherapy in patients with recurrent ovarian cancer.  J Clin Oncol 26: 2008 (May 20 suppl; abstr 5572).

5/Anwar K, Barnes MN, Kelly FJ, et. al. Safety and tolerability of a novel IL-12 gene therapeutic administered in combination with carboplatin/docetaxel in patients with recurrent ovarian cancer.  J Clin Oncol 28:15s, 2010 (suppl; abstr 5045).

Source: FDA Awards EGEN, Inc. Orphan -Drug Grant for Clinical Development of EGEN-001 for Treatment of Ovarian Cancer, Press Release, EGEN, Inc., February 2, 2011.

PARP Inhibitor MK-4827 Shows Anti-Tumor Activity in First Human Clinical Study

MK-4827, a new drug that targets proteins responsible for helping cancer cells repair their damaged DNA, has shown promising anti-tumor activity in its first human clinical trial.

MK-4827, a new drug that targets proteins responsible for helping cancer cells repair their damaged DNA, has shown promising anti-tumour activity in its first human clinical trial. Some patients with a range of solid tumors, many of whom had been treated unsuccessfully for their cancer with other therapies, have seen their tumors shrink or stabilize for periods of between 46 days to more than a year. The research will be presented today (Thursday) at the 22nd EORTC–NCI–AACR [1] Symposium on Molecular Targets and Cancer Therapeutics, which is being held in Berlin, Germany.

PARP is a key signaling enzyme involved in triggering the repair of single-strand DNA damage. PARP inhibition has been demonstrated to selectively kill tumor cells lacking components of the homologous recombination (HR) DNA repair pathway while sparing normal cells. Known defects in HR repair include the well-characterized hereditary BRCA1 and BRCA2 mutations in breast and ovarian cancer, as well as nonhereditary BRCA mutations. (Photo Credit: AstraZeneca Oncology)

Laboratory studies of the drug, MK-4827, have shown that it inhibits proteins called PARP1 and PARP2 (poly(ADP)-ribose polymerase). PARP is involved in a number of cellular processes and one of its important functions is to assist in the repair of single-strand breaks in DNA. Notably, if one single-strand DNA break is replicated (replication occurs before cell division), then it results in a double-strand break.  By inhibiting the action of PARP, double-strand breaks occur, which in turn, lead to cell death. Tumors that are caused by a mutation in the BRCA1 or BRCA2 genes are susceptible to cell death through PARP inhibition because correctly functioning BRCA genes assist in repairing double-strand DNA breaks via a process called homologous-recombination-dependent DNA repair, whereas mutated versions are unable to perform this role. Normal cells do not replicate as often as cancer cells and they still have homologous repair operating; this enables them to survive the inhibition of PARP and makes PARP a good target for anti-cancer therapy.

In a Phase I trial [2] conducted at the H. Lee Moffitt Cancer Center (Tampa Florida, USA), University of Wisconsin-Madison (Madison, USA) and the Royal Marsden Hospital (London, UK), MK-4827 was given to 59 patients (46 women, 13 men) with a range of solid tumors such as non-small cell lung cancer (NSCLC), prostate cancer, sarcoma, melanoma and breast and ovarian cancers. Some patients had cancers caused by mutations in the BRCA1/2 genes, such as breast and ovarian cancer, but others had cancers that had arisen sporadically.

Robert M. Wenham, M.D., MS, FACOG, Clinical Director, Gynecologic Oncology, Department of Women's Oncology, H. Lee Moffitt Cancer Center

The drug was given in pill form once a day, and the researchers found that the maximum tolerated dose was 300 mg per day. Dr. Robert Wenham, Clinical Director for Gynecologic Oncology in the Department of Women’s Oncology at the Moffitt Cancer Center, who is presenting data on behalf of the participating investigators, said: “MK-4827 is generally well tolerated, with the main dose-limiting toxicity being thrombocytopenia – an abnormal decrease in the number of platelets in the circulatory blood. The most common side effects are mild nausea, vomiting, anorexia and fatigue.”

The researchers saw anti-tumor responses in both sporadic (non-inherited) and BRCA1/2 mutation-associated cancers [emphasis added]. Ten patients with breast and ovarian cancers had partial responses, with progression-free survival between 51-445 days, and seven of these patients are still responding to treatment. Four patients (two with ovarian cancer and two with NSCLC) had stable disease for between 130-353 days.

Dr. Wenham said: “Most patients in the trial had exhausted standard therapies and those who responded to this drug have benefited. Several patients have been receiving treatment for more than a year. The responses mean that MK-4827 is working as hoped and justify additional studies. Just how well MK-4827 works compared to other treatments is the goal of the next set of studies.”

He gave a possible explanation as to why patients with cancers that were not caused by BRCA1 or BRCA 2 gene mutations also responded to the PARP inhibition. “BRCA is a tumor suppressor gene that assists in repairing double stranded DNA breaks. In BRCA-mutation related cancers, loss of both copies of the gene results in a non-functional protein and thus BRCA deficiency. Because BRCA works with other proteins, BRCA-pathway related deficiency can be seen in the absence of two mutated copies of the BRCA genes. This may explain why responses have been reported for this class of drugs in non-BRCA mutant cancers.”

Dr. Wenham and his colleagues are recruiting more patients for additional studies and an expansion of the existing trial. “We want to understand what types of cancers will respond best to treatment with MK-4827,” he said. “Cohorts are currently open for patients with ovarian cancer, patients without germ-line BRCA mutations, and prostate cancer patients. Cohorts will open soon for patients with T-cell prolymphocytic leukemia, endometrial cancer, breast cancer and colorectal cancer. MK-4827 is also being studied in combination with conventional chemotherapy drugs.”

Sources:

• PARP inhibitor, MK-4827, shows anti-tumour activity in first trial in humans. Abstract no: 362. 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Berlin, Germany, November 18, 2010.

• A Phase 1 Study of MK4827 in Patients With Advanced Solid Tumors, Clinical Trial Summary, ClinicalTrials.gov (NCT00749502).

Additional Information:

• A list of open ovarian cancer clinical trials involving the study of MK-4827, ClinicalTrials.gov.

• A list of open solid tumor clinical trials involving the study of MK-4827, ClinicalTrials.gov.

Related Information:

• New Assay Test Predicts That 50% of Ovarian Cancers Will Respond To In Vitro PARP Inhibition, by Paul Cacciatore, Libby’s H*O*P*E*™, November 11, 2010.

• PARP Inhibitor Olaparib Benefits Women With Inherited Ovarian Cancer Based Upon Platinum Drug Sensitivity, by Paul Cacciatore, Libby’s H*O*P*E*™, April 23, 2010.

References:

[1] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

[2] This study was funded by Merck & Co., Inc. MK-4827 is owned by Merck & Co., Inc.

PI3K Pathway: A Potential Ovarian Cancer Therapeutic Target?

…[T]here are several PI3K signaling pathway targeting drugs in clinical development for use against ovarian cancer and solid tumors, including GDC-0941, BEZ235, SF1126, XL-147, XL-765, BGT226, and PX-866.  The results of two recent medical studies suggest that the use of PI3K-targeted therapies may offer an effective therapeutic approach for patients with advanced-stage and recurrent ovarian cancer, including a generally chemotherapy-resistant histological subtype of epithelial ovarian cancer known as “ovarian clear cell cancer” (OCCC).  The targeting of the PI3K pathway in endometrial, ovarian, and breast cancer is also being investigated by a Stand Up To Cancer “Dream Team.” …

PI3K Cellular Signaling Pathway — An Overview

PI3K/AKT cellular signaling pathway (Photo: Cell Signaling Technology(R))

In 2004 and 2005, multiple researchers identified mutations in the PIK3CA  gene with respect to multiple cancers.[1]  The PIK3CA gene encodes the PI3K catalytic subunit p110α. PI3K (phosphoinositide 3- kinase) proteins have been identified in crucial signaling pathways of ovarian cancer cells. PI3Ks are also part of the PI3K-AKT-mTOR signaling pathway which promotes cellular glucose metabolism, proliferation, growth, survival, and invasion and metastasis in many cancers. PIK3CA gene mutations can increase PI3K signaling, thereby activating the PI3K-AKT-mTOR pathway within cancer cells.

As of this writing, there are several PI3K signaling pathway targeting drugs in clinical development for use against ovarian cancer and solid tumors, including GDC-0941, BEZ235, SF1126, XL-147, XL-765, BGT226, and PX-866. [2]  The results of two recent medical studies suggest that the use of PI3K-targeted therapies may offer an effective therapeutic approach for patients with advanced-stage and recurrent ovarian cancer, including a generally chemotherapy-resistant histological subtype of epithelial ovarian cancer known as “ovarian clear cell cancer” (OCCC).  The targeting of the PI3K pathway in endometrial, ovarian, and breast cancer is also being investigated by a Stand Up To Cancer “Dream Team.”

Frequent Mutation of PIK3CA Gene In Recurrent & Advanced Clear Cell Ovarian Cancer

OCCC is one of the five major subtypes of epithelial ovarian cancer. OCCC accounts for only 4% to 12% of epithelial ovarian cancer in Western countries and, for unknown reasons, it comprises more than 20% of such cancers in Japan [3,4,5]. OCCC possesses unique clinical features such as a high incidence of stage I disease, a large pelvic mass, an increased incidence of venous thromboembolic complications, and hypercalcemia. It is frequently associated with endometriosis.  Compared to serous ovarian cancer, OCCC is relatively resistant to conventional platinum and taxane-based chemotherapy. For these reasons, new effective therapies are desperately needed for OCCC.

Researchers from Johns Hopkins and the University of California, Los Angeles (UCLA) analyzed 97 OCCC tumors for genetic sequence mutations in KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog), BRAF (v-raf murine sarcoma viral oncogene homolog B1), PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide), TP53 (tumor protein p53), PTEN (phosphatase and tensin homolog), and CTNNB1 (Catenin, Beta-1) as these mutations frequently occur in other major types of ovarian cancers.[6] The samples tested included the following:

• 18 OCCCs for which affinity-purified tumor cells from fresh specimens were available;

• 69 microdissected OCCC tumors from paraffin tissues; and

• 10 OCCC tumor cell lines.

Upon test completion, the researchers discovered that sequence mutations of PIK3CA, TP53, KRAS, PTEN, CTNNB1, and BRAF occurred in 33%, 15%, 7%, 5%, 3%, and 1% of OCCC cases, respectively.

Clear cell carcinoma of the ovary (Photo: Geneva Foundation For Medical Education & Research)

The sequence analysis of the 18 affinity purified OCCC tumors and the 10 OCCC cell lines showed a PIK3CA mutation frequency of 46%. Based upon these findings the researchers concluded that the use of PIK3CA-targeting drugs may offer a more effective therapeutic approach compared with current chemotherapeutic agents for patients with advanced-stage and recurrent OCCC. As noted above, there are several PI3K-targeting drugs in clinical development for use against ovarian cancer and solid tumors.[2]

Notably, one of the researchers involved with this OCCC study is Dennis J. Slamon, M.D., Ph.D. Dr. Slamon serves as the Director of Clinical/Translational Research, and as Director of the Revlon/UCLA Women’s Cancer Research Program at the Jonsson Comprehensive Cancer Center. Dr. Slamon is also a professor of medicine, chief of the Division of Hematology/Oncology and Executive Vice Chair of Research for UCLA’s Department of Medicine. Dr. Slamon is a co-discoverer of the breast cancer drug Herceptin®. Herceptin is a monoclonal antibody targeted therapy used against HER-2 breast cancer, an aggressive breast cancer subtype that affects 20% to 30% of women with the disease. Herceptin’s development was based, in part, upon the unique genetic profile of HER-2 breast cancer as compared to other forms of breast cancer. Herceptin® revolutionized the treatment of HER-2 postive breast cancer and is recognized worldwide as the standard of care for that subtype of breast cancer.  The approach taken by Johns Hopkins and UCLA researchers in this study — the identification of  a subtype within a specific form of cancer that may be susceptible to a targeted therapy —  bears a striking similarity to the overarching approach taken in the development of Herceptin®.

Ovarian Cancer & Other Solid Tumors With PIK3CA Gene Mutations Respond To PI3K-AKT-mTOR Pathway Inhibitors In Phase I Clinical Testing.

Testing patients with cancer for PIK3CA gene mutations is feasible and may allow targeted treatment of the PI3K-AKT-mTOR cellular signaling pathway, according to the results of a University of  Texas, M.D. Anderson Cancer Center study presented on November 17, 2009 at the 2009 AACR (American Association for Cancer Research)-NCI (National Cancer Institute)-EORTC (European Organization For Research & Treatment of Cancer) International Conference on Molecular Targets and Cancer Therapeutics.[7]

mTOR cellular signaling pathway (Photo: Cell Signaling Technology(R))

Filip Janku, M.D., Ph.D, a clinical research fellow with the M.D. Anderson Cancer Center’s department of investigational cancer therapeutics, and colleagues conducted a mutational analysis of exon 9 and exon 20 of the PI3KCA gene using DNA from the tumors of patients referred to targeted therapy clinical trials. Patients with PIK3CA mutations were preferably treated whenever possible with regimens utilizing PI3K-AKT-mTOR signaling pathway inhibitors.

As part of this study 117 tumor samples were analyzed. PIK3CA mutations were detected in 14 (12%) patients.  In tumor types with more than 5 patients tested, PIK3CA mutations were identified in endometrial cancer (43%, 3 out of 7 patients), ovarian cancer (22%, 5 out of 23 patients), squamous head and neck cancer (14%, 1 out of 7 patients), breast cancer (18%, 2 out of 11 patients), and colon cancer (15%, 2 out of 13 patients). No mutations were identified in patients with melanoma or cervical cancer.

Of the 14 patients found to possess PIK3CA mutations, 10 were treated based upon a clinical trial protocol that included a drug targeting the PI3K-AKT-mTOR pathway.  A partial response to treatment was experienced by 4 (40%) patients. Although the total number of patients is small, there were 2 (67%) patient responses in 3 endometrial cancer cases, 1 (25%) patient response in 4 ovarian cancer cases, 1 (100%) patient response in 1 breast cancer, and no patient response in 1 colorectal cancer case.  Although the total number of study patients is small, the researchers conclude that the response rate appears high (40%) in tumors with PIK3CA mutations treated with PI3K-AKT-mTOR pathway inhibitors.

“The implications of this study are twofold,” said Dr. Janku.  “We demonstrated that PIK3CA testing is feasible and may contribute to the decision-making process when offering a patient a clinical trial. Although this study suffers from low numbers, the response rate observed in patients treated with inhibitors of PI3K/AKT/mTOR pathway based on their mutational status was well above what we usually see in phase-1 clinical trials.”  “These results are intriguing but at this point should be interpreted with caution,” said Janku. “The promising response rate needs to be confirmed in larger groups of patients. We expect to learn more as this project continues to offer PIK3CA screening to patients considering a phase-1 clinical trial.”

Stand Up 2 Cancer Dream Team: Targeting the PI3K Pathway in Women’s Cancers

The potential importance of the PI3K pathway in the treatment of ovarian cancer is emphasized by the two medical studies above.  This issue is also receiving considerable attention from one of the Stand Up 2 Cancer (SU2C) “Dream Teams,” which is going to evalute  the potential for targeting the PI3K pathway in women’s cancer.  SU2C assigned $15 million of cancer research funding to this critical issue.  The scientists involved in this SU2C Dream Team are the pioneers who discovered the PI3K pathway and validated its role in human cancers, and they will focus on breast, ovarian and endometrial cancers, all of which possess the PI3K mutation.

The leader and co-leaders of the PI3K pathway SU2C team are set forth below.

Leader:

Lewis C. Cantley, Ph.D., Director, Cancer Center at Beth Israel Deaconess Medical Center.

Co-Leaders:

Charles L. Sawyers, M.D., Director, Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center.

Gordon B. Mills, M.D., Ph.D., Chair, Department of Systems Biology, University of Texas, M.D. Anderson Cancer Center.

The specific SU2C Dream Team research goal with respect to targeting the PI3K pathway in women’s cancers is stated as follows:

The PI3K pathway is mutated in more cancer patients than any other, and these mutations are the most frequent events in women’s cancers, making it an attractive molecular target for agents that inhibit these genetic aberrations. If successful, this project will allow clinicians to use biomarkers and imaging techniques to predict which patients will benefit from PI3K pathway inhibitors and lead to the development of therapeutic combinations that will hit multiple targets in the complex pathways that contribute to cancer cell growth.  This work will help assure that these therapies are given to patients who will benefit from them, and it will also increase the overall pace of clinical trials targeting PI3K inhibitors.

Based upon the two studies discussed, and the creation and funding of the SU2C Dream Team for the purpose of targeting the PI3K pathway in women’s cancer, the future holds great promise in the battle against ovarian cancer (including OCCC).  It is our hope that more clinical study investigators will offer PI3K pathway mutation screening to all ovarian cancer patient volunteers.  Libby’s H*O*P*E*™ will continue to monitor the clinical development of PI3K pathway inhibitors, and make our readers aware of all future developments.

________________________________

References:

1/Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene. 2008 Sep 18;27(41):5497-510. PubMed PMID: 18794884
Samuels Y, Ericson K. Oncogenic PI3K and its role in cancer. Curr Opin Oncol. 2006 Jan;18(1):77-82. PubMed PMID: 16357568.
Levine DA, Bogomolniy F, Yee CJ, et. al. Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin Cancer Res. 2005 Apr 15;11(8):2875-8. PubMed PMID: 15837735.
Samuels Y, Wang Z, Bardelli A, et. al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004 Apr 23;304(5670):554. Epub 2004 Mar 11. PubMed PMID: 15016963.

2/For open ovarian cancer clinical trials using a PI3K-targeted therapy; CLICK HERE; For open solid tumor clinical trials using a PI3K-targeted therapy, CLICK HERE.

3/ Itamochi H, Kigawa J & Terakawa N.  Mechanisms of chemoresistance and poor prognosis in ovarian clear cell carcinoma. Can Sci 2008 Apr;99(4):653-658. [PDF Document]

4/Schwartz DR, Kardia SL, Shedden KA, et. al.  Gene Expression in Ovarian Cancer Reflects Both Morphology and Biological Behavior, Distinguishing Clear Cell from Other Poor-Prognosis Ovarian Carcinomas.  Can Res 2002 Aug; 62, 4722-4729.

5/Sugiyama T & Fujiwara K.  Clear Cell Tumors of the Ovary – Rare Subtype of Ovarian Cancer, Gynecologic Cancer, American Society of Clinical Oncology (ASCO) Educational Book, 2007 ASCO Annual Meeting, June 2, 2007 (Microsoft Powerpoint presentation).

6/Kuo KT, Mao TL, Jones S, et. al. Frequent Activating Mutations of PIK3CA in Ovarian Clear Cell Carcinoma. Am J Pathol. 2009 Apr 6. [Epub ahead of print]

7/Janku F, Garrido-Laguna I, Hong D.S.  PIK3CA mutations in patients with advanced cancers treated in phase I clinical trials, Abstract #B134, Molecular Classification of Tumors, Poster Session B, 2009 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference. [PDF Document].

Unusual Metals May Forge New Ovarian & Colon Cancer Drugs

Drugs made using unusual metals could form an effective treatment against colon and ovarian cancer, including cancerous cells that have developed immunity to other drugs, according to research at the University of Warwick and the University of Leeds.

Drugs made using unusual metals could form an effective treatment against colon and ovarian cancer, including cancerous cells that have developed immunity to other drugs, according to research at the University of Warwick and the University of Leeds.

Professor Peter Sadler of the University of Warwick. (Photo: University of Warwick)

The study, published in the Journal of Medicinal Chemistry, showed that a range of compounds containing the two transition metals Ruthenium and Osmium, which are found in the same part of the periodic table as precious metals like platinum and gold, cause significant cell death in ovarian and colon cancer cells.

The compounds were also effective against ovarian cancer cells which are resistant to the drug Cisplatin, the most successful transition metal drug, which contains the metal platinum.

Dr Patrick McGowan, one of the lead authors of the research from the School of Chemistry at the University of Leeds, explains: “Ruthenium and Osmium compounds are showing very high levels of activity against ovarian cancer, which is a significant step forward in the field of medicinal chemistry.

Sabine H. van Rijt, lead researcher in the laboratory of Professor Peter Sadler in the Department of Chemistry at the University of Warwick, said:  “Most interestingly, cancerous cells that have shown resistance to the most successful transition metal drug, Cisplatin, show a high death rate with these new compounds.”

Professor Sadler, at the University of Warwick, commented that he is “excited by the novel design features in these compounds which might enable activity to be switched on and off”.

Cisplatin was discovered in the 1970s and is one of the most effective cancer drugs on the market, with a 95% cure rate against testicular cancer.  Since the success of Cisplatin, chemists all over the world have been trying to discover whether other transition metal compounds can be used to treat cancer.

In this type of anti-cancer drug transition metal atoms bind to DNA molecules which trigger apoptosis, or programmed cell death, in the cancerous cells.

The study is a collaboration between the universities of Warwick and Leeds and was funded by the Engineering and Physical Sciences Research Council (EPSRC).

Sources:

• Unusual metals could forge new cancer drugs, Press Release, University of Warwick, Coventry, U.K., October 19, 2009.

• van Rijt, SH, Hebden AJ, Amaresekera T, et. al. Amide Linkage Isomerism As an Activity Switch for Organometallic Osmium and Ruthenium Anticancer Complexes. Journal of Medicinal Chemistry, 2009; 090930083513062 DOI: 10.1021/jm900731j.

Novel Targeted Gene Therapies Use Diphtheria Toxin To Fight Ovarian Cancer; One Clinical Trial Underway

Two separate research teams reported promising results last week based upon preclinical studies involving the use of diphtheria toxin to fight ovarian cancer. … A targeted gene therapy was utilized in both studies, wherein a gene fragment capable of producing diptheria toxin was combined with a nanoparticle which was targeted against a unique or overexpressed genetic characteristic of the ovarian cancer tumor cells. Both research teams reported significant reduction in ovarian cancer tumor mass and extended survival for the treated mice. Based upon these findings, one research team already announced the opening of a Phase I/II clinical trial which will test the novel therapy on patients with advanced stage ovarian cancer.

Targeted Gene Therapy In the Fight Against Ovarian Cancer

The peritoneal cavity is a common site of ovarian cancer and accompanying ascites caused by the disease. Ascites is an abnormal buildup of fluid in the peritoneal cavity that causes swelling.  Malignant tumor cells may be found in the ascites fluid in connection with late stage ovarian cancer.  Massive ascites and the related abdominal distention can cause anorexia, nausea, vomiting and respiratory difficulties, and negatively impact the patient’s quality of life. Ovarian cancer patients frequently experience disease involvement of the pelvic and retroperitoneal lymph nodes as well. The standard primary treatment of patients with advanced stage ovarian cancer is cytoreductive surgery followed by platinum drug and taxane drug doublet chemotherapy. Despite this aggressive approach, there is a high rate of disease recurrence. Although discovery of several other active nonplatinum cytotoxic agents has improved outcome, long-term survival rates are low. Success of traditional chemotherapy has been limited by drug resistance and lack of specificity with respect to disease formation and progression. Thus, novel “targeted” ovarian cancer therapies that achieve improved long-term disease control with lower toxicity are desperately needed.

A so-called “targeted therapy” utilizes drugs or other medically manufactured substances (e.g., small molecule drugs or monoclonal antibodies) to block the growth and spread of cancer by interfering with specific molecules involved in cancer tumor growth and progression.  By identifying and selectively focusing upon molecular and cellular changes or unique genetic characteristics that are specific to cancer, targeted cancer therapies may be more effective than other types of treatment, including chemotherapy, and less harmful to normal cells.

It is possible for a targeted therapy to incorporate a gene therapy. Gene therapy is an experimental treatment that involves the introduction of genetic material (DNA or RNA) into a human cell to fight a disease such as cancer.  When both therapeutic approaches are combined by researchers, a “targeted gene therapy” is the result.  A targeted gene therapy is an attractive approach to controlling or killing human cancer cells only if the therapy can selectively identify and exploit the genetic and epigenetic alterations in cancer cells, without harming normal cells that do not possess such alternations.

Two separate research groups reported promising results last week based upon preclinical studies involving the use of diphtheria toxin to fight ovarian cancer.  The toxin is produced by a deadly bacterium (Corynebacterium diphtheriae).  A targeted gene therapy was utilized in both studies, wherein a gene fragment capable of producing diptheria toxin was combined with a nanoparticle which was targeted against a unique or overexpressed genetic characteristic of the ovarian cancer tumor cells.  Both research teams reported significant reduction in ovarian cancer tumor mass and extended survival for the treated mice. Based upon these findings, one research team already announced the opening of a Phase I/II clinical trial which will test the novel therapy on patients with advanced stage ovarian cancer.

MIT-Lankenau Institute Researchers Use Diphtheria Toxin Gene Therapy To Target Overexpression Of The MSLN & HE4 Ovarian Cancer Genes.

Daniel Anderson, Ph.D., Research Associate, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

The first study, which appears in the August 1 issue of the journal Cancer Research, was conducted by a team of researchers from the Massachusetts Institute of Technology (MIT) and the Lankenau Institute of Medical Research (Lankenau Institute). In this study, the researchers used a nanoparticle as a delivery vehicle (or vector) for DNA that encodes a diphtheria toxin suicide protein (DT-A).  The novel nanoparticles are made with positively charged, biodegradable polymers known as poly(beta-amino esters). When mixed together, these polymers can spontaneously assemble with DNA to form nanoparticles. The polymer-DNA nanoparticle can deliver functional DNA when injected into or near the targeted tissue.

The nanoparticle carrying the DT-A is designed to target overexpression of two genes (mesothelin (MSLN) and HE4 (or WFDC2)) that are highly active in ovarian tumor cells, but not in normal cells. Once inside an ovarian cancer tumor cell, the DT-A disrupts the tumor cell’s ability to manufacture critical life sustaining proteins, thereby causing cell death.  Accordingly, the choice of the DT-A fragment of a diptheria toxin gene ensures high ovarian cancer cell killing activity.  It also avoids unintended toxicity to normal cells because the DT-A released from destroyed ovarian cancer cells is not able to enter normal neighboring tissue cells in the absence of the DT-B fragment which was excluded from the original nanoparticle delivery system or vector.

As part of this study, researchers administered DT-A nanoparticles directly into the peritoneal cavity – which encases abdominal organs such as the stomach, liver, spleen, ovaries and uterus – of mice xenografted with primary and metastatic ovarian tumors.  Ovarian cancer is known to initially spread throughout the peritoneal cavity, and current therapeutic approaches in humans include direct injection into the peritoneal space, thereby targeting the therapy to the ovaries and nearby tissues where tumors may have spread.

“… [The researchers] discovered that the intraperitoneal (IP) administration of DT-A nanoparticles resulted in a significant reduction in ovarian tumor mass and extended survival for the treated mice.  The researchers also found that the targeted gene-therapy treatment was as effective, and in some cases more effective, than the traditional chemotherapy combination of cisplatin and paclitaxel. …”

Robert S. Langer is the David H. Koch Institute for Integrative Cancer Research Professor (there are 14 Institute Professors at MIT; being an Institute Professor is the highest honor that can be awarded to a faculty member). Dr. Langer has written approximately 1,050 articles. He also has approximately 750 issued and pending patents worldwide. Dr. Langer’s patents have been licensed or sublicensed to over 220 pharmaceutical, chemical, biotechnology and medical device companies. He is the most cited engineer in history.

Janet Sawicki, Ph.D., Professor, Lankenau Institute of Medical Research. Dr. Sawicki also serves as an Associate Professor at the Kimmel Cancer Center of Thomas Jefferson University. Her ovarian cancer research is funded by the National Institutes of Health, the U.S. Department of Defense, the Sandy Rollman Foundation, the Teal Ribbon Ovarian Cancer Foundation, and the Kaleidoscope of Hope Foundation.

Daniel Anderson, Ph.D., research associate in the David H. Koch Institute for Integrative Cancer Research at MIT and a senior author of the paper, and others from MIT, including Institute Professor Robert Langer, along with researchers from the Lankenau Institute, led by Professor Janet Sawicki, discovered that the intraperitoneal (IP) administration of DT-A nanoparticles resulted in a significant reduction in ovarian tumor mass and extended survival for the treated mice.  The researchers also found that the targeted gene-therapy treatment was as effective, and in some cases more effective, than the traditional chemotherapy combination of cisplatin and paclitaxel. Furthermore, the novel therapy did not have the toxic side effects of chemotherapy because the diptheria toxin gene is engineered to function in ovarian cells but is inactive in normal cell types.

Based upon these finding, the MIT and Lankenau Institute researchers concluded that IP administration of DT-A nanoparticles, combined with designed targeting of those nanoparticles against ovarian tumor cell gene (MSLN & HE4) expression, holds promise as an effective therapy for advanced-stage ovarian cancer. According to Anderson, human clinical trials could start, after some additional preclinical studies, in about 1 to 2 years.  Currently ovarian cancer patients undergo surgery followed by chemotherapy. In many cases, the cancer returns after treatment.  Disease recurrence is problematic because there are no curative therapies for advanced-stage tumors.

For several years, the MIT-Lankenau Institute team worked to develop the DT-A nanoparticles as an alternative to viruses, which are associated with safety risks. In addition to ovarian cancer, these nanoparticles have demonstrated treatment potential for a variety of diseases, including prostate cancer and viral infection. “I’m so pleased that our research on drug delivery and novel materials can potentially contribute to the treatment of ovarian cancer,” Langer said. In future studies, the team plans to examine the effectiveness of nanoparticle-delivered diphtheria toxin genes in other types of cancer, including brain, lung and liver cancers.

Other MIT authors of the paper are recent MIT Ph.D. recipients Gregory Zugates and Jordan Green (now a professor at John’s Hopkins University), and technician Naushad Hossain. The research was funded by the Department of Defense and the National Institutes of Health.

Israeli Researchers Use Diphtheria Toxin Gene Therapy To Target Overexpression Of The H19 Ovarian Cancer Gene.

The second study was conducted by Israeli researchers and was published August 6 online ahead of print in the Journal of Translational Medicine.

In the provisional study report, the researchers note that based upon earlier studies from their team and others, the H19 gene has emerged as a candidate for cancer gene therapy. The H19 gene is expressed at substantial levels in ovarian cancer tumor cells, but is nearly undetectable in surrounding normal tissue cells.  Although the Israeli research team acknowledges that the exact function of H19 is the subject of past debate, it notes that recent data suggests a role for H19 in promoting cancer progression, angiogenesis and metastasis.

As a first step, Israeli researchers tested H19 gene expression in ovarian cancer cells obtained from the ascites fluid of 24 patients, and established that H19 expression levels were detected in 90% of the tested patients. Of those patients with positive H19 expression, 76% showed a moderate or high level of expression, while 24% showed a low level of expression.

Next, the researchers created a DT-A nanoparticle similar to the one created by the MIT/Lankenau research team as described above, except the Israeli nanoparticle was designed to target H19 overexpression within ovarian cancer cells.  The therapeutic effect of the DT-A/H19 nanoparticles was first tested in vitro against various ovarian cancer cell lines and cells obtained from patient ascites fluid.  The researchers determined that the DT-A/H19 nanoparticle therapy caused ovarian cancer cell death.  The therapeutic effect of the DT-A nanoparticles was tested in vivo by injecting the DT-A nanoparticles into mice xenografted with ovarian cancer tumors. The researchers estimate that the DT-A nanoparticle therapy reduced ovarian cancer tumor growth in the treated mice by 40%.

Based upon these finding, the researchers note that although the study report issued is provisonal, it is their working hypothesis that intraperitoneal administration of DT-A/H19 nanoparticles holds the potential to (1) reach ascites tumor cells, (2) deliver its intracellular toxin without targeting normal tissue cells, and (3) reduce tumor burden & fluid accumulation; and therefore, improve the patient’s quality of life, and hopefully, prolong her survival.

• DT-A/H19 Nanoparticle Therapy Administered To An Israeli Patient On A Compassionate Use Trial Basis

In the provisional study report, the researchers state that the targeted gene therapy was administered to an Israeli patient with advanced, recurrent ovarian cancer, who qualified for compassionate use treatment under Israeli regulatory rules.  Specifically, the patient’s intraperitoneal ovarian cancer metastases and ascites were treated with the DT-A/H19 nanoparticle therapy after the failure of conventional chemotherapy. The results of the single patient compassionate use trial suggest that the drug caused no serious adverse events at any drug dosage level.  Moreover, the patient experienced (1) a 50% decrease in serum cancer marker protein CA-125, (2) a significant decrease in the number of cancerous cells in the ascites, and (3) a clinical improvement as reported by her doctors.  It is reported that the patient’s quality of life increased during the course of treatment and her condition continues to be stable, with no new cancerous growths.

• Phase I/II Clinical Trial To Test DT-A/H19 Nanoparticle Therapy (BC-819) In the U.S. & Israel

The DT-A/H19 nanoparticle therapy is being developed commercially by BioCancell Therapeutics, Inc (BioCancell) Recently, BioCancell announced the opening of a clinical trial to test the DT-A/H19 nanoparticle therapy (also referred to as BC-819) in patients with advanced stage ovarian cancer.  The clinical trial is entitled, Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intraperitoneal Administration of DTA-H19 in Subjects With Advanced Stage Ovarian Cancer, and the trial investigators are recruiting patients in the U.S. and Israel as indicated below.

University of Pennsylvania Medical Center [Abramson Cancer Center] (Recruiting)
Philadelphia, Pennsylvania, United States, 19104-6142
Contact: Lana E. Kandalaft, Pharm.D, PhD – 215-537-4782 (lknd@mail.med.upenn.edu)
Principal Investigator: George Coukos, M.D., Ph.D.

Massey Cancer Center (Not yet recruiting)
Richmond, Virginia, United States, 23298-0037
Contact: Jane W. Baggett, RN 804-628-2360 (jbaggett@mcvh-vcu.edu)
Principal Investigator: Cecelia H. Boardman, M.D.

The Edith Wolfson Medical Center (Recruiting)
Holon, Israel
Contact: Pnina Nir (972)-52-8445143 (pninanir@wolfson.health.gov.il)
Principal Investigator: Tally Levy, M.D.

Hadassah University Hospital (Recruiting)
Jerusalem, Israel
Contact: Zoya Bezalel (972)-2-6776725 (zoyab@hadassah.org.il)
Principal Investigator: David Edelman, MD

Meir Hospital (Recruiting)
Kfar Saba, Israel
Contact: Tal Naderi 09-7472213 (Ta.INadiri@clalit.org.il)
Principal Investigator: Ami Fishman, MD

In the provisional study report, the Israeli researchers discuss the importance of collecting data regarding the correlation between the level of ovarian cancer cell H19 expression and the efficacy of the treatment as part of the clinical trial discussed above.  Based upon accrued future clinical trial data, the researchers believe that they will be able to identify in advance patients that will respond to this novel therapy, as well as non-responders who are resistant to all known therapies, thereby avoiding treatment failure and unnecessary suffering and cost.

References:

• Nanoparticles target ovarian cancer – New gene therapy technique could fight late-stage tumors, MIT News, Massachusetts Institute of Technology, 30 Jul. 09.

• Huang YH, Zugates GT, Peng W, et. al. Nanoparticle-delivered suicide gene therapy effectively reduces ovarian tumor burden in mice. Cancer Res. 2009 Aug 1;69(15):6184-91.

• Mizrahi A, Czerniak A, Levy T, et. al. Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. J Transl Med. 2009 Aug 6;7(1):69. [Epub ahead of print][Provisional Study Full Text – PDF Adobe Reader Document]

• Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intraperitoneal Administration of DTA-H19 in Subjects With Advanced Stage Ovarian Cancer, Clinical Trial Summary, http://www.ClinicalTrials.gov, First Received: January 18, 2009 Last Updated: June 12, 2009.

• Ovarian Cancer – Phase I/IIa Clinical Trial of BC-819 [DTA-H19], Clinical Trial Description, BioCancell Therapeutics, Inc.

Beyond BRCA1 & BRCA2: U.K. Researchers Identify Genetic Defect That Could Increase Risk of Ovarian Cancer Up To 40%

Scientists have located a region of DNA which – when altered – can increase the risk of ovarian cancer according to research published in Nature Genetics today. An international research group led by scientists based at the Cancer Research UK Genetic Epidemiology Unit, at the University of Cambridge and UCL (University College London) searched through the genomes of 1,810 women with ovarian cancer and 2,535 women without the disease from across the UK. …The scientists estimate that there is a 40 per cent increase in lifetime risk for women carrying the DNA variation on both copies of chromosome nine compared with someone who doesn’t carry it on either chromosome. The risk for women carrying the variation on both chromosomes is 14 in 1000 – compared with [10] ten in 1000 [in the general population]. … The lifetime risk for a woman carrying the DNA variant on one copy of the chromosome is increased by 20 per cent from ten in 1000 to 12 in 1000. …

Genetic link to ovarian cancer found

Cancer Research UK

SUNDAY 2 AUGUST 2009

Cancer Research UK Press Release

Scientists have located a region of DNA which – when altered – can increase the risk of ovarian cancer according to research published in Nature Genetics today.

An international research group led by scientists based at the Cancer Research UK Genetic Epidemiology Unit, at the University of Cambridge and UCL (University College London) searched through the genomes of 1,810 women with ovarian cancer and 2,535 women without the disease from across the UK. They analysed 2.5 million variations in DNA base pairs – the letters which spell out the genetic code – to identify common spelling ‘errors’ linked to ovarian cancer risk.

The scientists identified the genetic ‘letters’- called single nucleotide polymorphisms (SNPs) – which when spelled slightly differently increase ovarian cancer risk in some women. This is the first time scientists have found a SNP linked uniquely to risk of ovarian cancer and is the result of eight years of investigations. With the help of the international Ovarian Cancer Association Consortium (OCAC), they then looked at more than 7,000 additional women with ovarian cancer and 10,000 women without disease from around the world to confirm this finding.

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The region of risk DNA is located on chromosome nine – there are 23 pairs of each chromosome in humans, one of each pair inherited from each parent. The scientists estimate that there is a 40 per cent increase in lifetime risk for women carrying the DNA variation on both copies of chromosome nine compared with someone who doesn’t carry it on either chromosome. The risk for women carrying the variation on both chromosomes is 14 in 1000 – compared with [10] ten in 1000 [in the general population].

Approximately 15 per cent of women in the UK population carry two copies of the variant DNA.

The lifetime risk for a woman carrying the DNA variant on one copy of the chromosome is increased by 20 per cent from ten in 1000 to 12 in 1000. Approximately 40 per cent of women in the UK carry one copy.

Senior author Dr. Simon Gayther, whose work is supported by Cancer Research UK and The Eve Appeal charity which fundraises for the gynaecological cancer research team based at UCL, said: “The human DNA blueprint contains more than 10 million genetic variants. These are part and parcel of our characteristics and make-up – but a handful will also increase the chances of some women getting ovarian cancer and we have found the first one of these.”

“There is now a genuine hope that as we find more, we can start to identify the women at greatest risk and this could help doctors to diagnose the disease earlier when treatment has a better chance of being successful.”

Dr. Andrew Berchuck, head of the international Ovarian Cancer Association Consortium steering committee, said: “This study confirms that ovarian cancer risk is partly determined by genetic variants present in a large number of women. This initial discovery and others that will likely follow in the future lay the groundwork for individualised early detection and prevention approaches to reduce deaths from ovarian cancer.”

Ovarian cancer is the fifth most common cancer in women in the UK with around 6,800 new cases diagnosed each year in the UK – 130 women every week. It is the fourth most common cause of cancer death in women in the UK with around 4,300 deaths from the disease in the UK each year.

BRCA1 and BRCA2 are high risk genes which cause breast cancer and are already known to significantly increase the risk of ovarian cancer- but faults in these genes are rare and probably cause less than five per cent of all cases of ovarian cancer.

Lead author, Professor Dr Paul Pharoah, a Cancer Research UK senior research fellow at the University of Cambridge, said: “We already know that people with mistakes in the BRCA1 and BRAC2 genes have a greater risk of ovarian cancer – but on their own they don’t account for all of the inherited risk of the disease. “It is likely that the remaining risk is due to a combination of several unidentified genes – which individually carry a low to moderate risk. Now we have ticked one off, the hunt is on to find the rest.”

Rose Lammy, the mother of David Lammy MP [Member of Parliament] for Tottenham and Minister for Higher Education and Intellectual Property, died of ovarian cancer in 2008. Rose Lammy’s DNA sample was included in the study, and she carried both risk alleles of the new genetic marker that researchers have identified.

David Lammy said: “I am pleased that Mum’s sample was included in this study as it is one step towards earlier diagnosis of ovarian cancer when treatment is more successful. We now know the fact that she had this altered DNA meant that her lifetime risk had risen from 10 in 1,000 to 14 in 1,000, an increase of 40 per cent compared to those women who don’t carry this DNA variation. Dr Lesley Walker, director of cancer information at Cancer Research UK, added: “This is an important discovery. Our researchers have worked as part of a huge collaboration to establish the regions of DNA that can increase someone’s risk of developing ovarian cancer. “This research paves the way for scientists to discover even more genes linked to ovarian cancer and could lead to new approaches to treat or prevent the disease – crucially it will help doctors manage women who are at increased risk.”

Source: Genetic link to ovarian cancer found, Cancer Research U.K. Press Release & Video, 02 Aug. 09.

Reference: Honglin Song et al. (2009). A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2 Nature Genetics 10.1038/ng.424.

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.

Senators Kennedy & Hutchison Renew War On Cancer

On March 26, 2009, Senators Edward M. Kennedy (D-Massachusetts) and Kay Bailey Hutchison (R-Texas) introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling cancer. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Senator Kennedy. The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

Edward M. Kennedy, U.S. Senator For The Commonwealth of Massachusetts

On March 26, 2009, Senators Edward M. Kennedy (D-Massachusetts) and Kay Bailey Hutchison (R-Texas) introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling cancer. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Senator Kennedy. The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

We provide below the full text of the following documents:

• Kennedy On The Introduction of the 21st Century ALERT Act, As Entered Into the Congressional Record, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• Kennedy Renews the War Against Cancer, Press Release, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• 21st Century Cancer ALERT Act, Senators Kennedy and Hutchinson, Section by Section Summary, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• Renewing the War on Cancer, by Edward M. Kennedy and Kay Bailey Hutchinson, Op-Ed., Houston Chronicle, March 26, 2009.

• S. 717: 21st Century Cancer ALERT (Access to Life-Saving Early detection, Research and Treatment) Act, 111th Congress,www.govtrack.us (Full text of bill as of April 13, 2009).  CLICK HERE for Adobe Reader PDF document.

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KENNEDY ON THE INTRODUCTION OF THE 21st Century ALERT Act

As Entered into the [Congressional] Record

March 26, 2009

FOR IMMEDIATE RELEASE

Thirty seven years ago, a Republican President and Democratic Congress came together in a new commitment to find a cure for cancer. At the time, a cancer diagnosis meant almost certain death. In 1971, we took action against this deadly disease and passed the National Cancer Act with broad bipartisan support, and it marked the beginning of the War on Cancer.

Since then, significant progress has been made. Amazing scientific research has led to methods to prevent cancer, and treatments that give us more beneficial and humane ways to deal with the illness. The discoveries of basic research, the use of large scale clinical trials, the development of new drugs, and the special focus on prevention and early detection have led to breakthroughs unimaginable only a generation ago.

As a result, cancer today is no longer the automatic death sentence that it was when the war began. But despite the advances we have made against cancer, other changes such as aging of the population, emerging environmental issues, and unhealthy behavior, have allowed cancer to persist. The lives of vast numbers of Americans have been touched by the disease. In 2008, over 1.4 million Americans were diagnosed with some form of cancer, and more than half a million lost their lives to the disease.

The solution isn’t easy but there are steps we can and must take now, if we hope to see the diagnosis rate decline substantially and the survival rate increase in the years ahead. The immediate challenge we face is to reduce the barriers that obstruct progress in cancer research and treatment by integrating our current fragmented and piecemeal system of addressing the disease.

Last year, my colleague Senator Hutchison and I agreed that to build on what the nation has accomplished, we must launch a new and more urgent war on cancer. The 21st Century Cancer ALERT Act we are introducing today will accelerate our progress by using a better approach to fighting this relentless disease. Our goal is to break down the many barriers that impede cancer research and prevent patients from obtaining the treatment that can save their lives.

We must do more to prevent cancer, by emphasizing scientifically proven methods such as tobacco cessation, healthy eating, and exercise. Healthy families and communities that have access to nutritious foods and high quality preventive health care will be our best defense against the disease. I’m confident that swift action on national health reform will make our vision of a healthier nation a reality. Obviously, we cannot prevent all cancers, so it is also essential that the cancers that do arise be diagnosed at an initial, curable stage, with all Americans receiving the best possible care to achieve that goal.

We cannot overemphasize the value of the rigorous scientific efforts that have produced the progress we have made so far. To enhance these efforts, our bill invests in two key aspects of cancer research– infrastructure and collaboration of the researchers. We include programs that will bring resources to the types of cancer we least understand. We invest in scientists who are committed to translating basic research into clinical practice, so that new knowledge will be brought to the patients who will most benefit from it.

One of the most promising new breakthroughs is in identifying and monitoring the biomarkers that leave enough evidence in the body to alert clinicians to subtle signs that cancer may be developing. Biomarkers are the new frontier for improving the lives of cancer patients because they can lead to the earliest possible detection of cancer, and the Cancer ALERT Act will support the development of this revolutionary biomarker technology.

In addition, we give new focus to clinical trials, which have been the cornerstones of our progress in treating cancer in recent decades. Only through clinical trials are we able to discover which treatments truly work. Today, however, less than 5% of cancer patients currently are enrolled in clinical trials, because of the many barriers exist that prevent both providers and patients from participating in these trials. A primary goal of our bill is to begin removing these barriers and expanding access to clinical trials for many more patients.

Further, since many cancer survivors are now living longer lives, our health systems must be able to accommodate these men and women who are successfully fighting against this deadly disease. It’s imperative for health professionals to have the support they need to care for these survivors. To bring good lifelong care to cancer survivors, we must invest more in research to understand the later effects of cancer and how treatments affect survivors’ health and the quality of their lives.

We stand today on the threshold of unprecedented new advances in this era of extraordinary discoveries in the life sciences, especially in personalized medicine, early diagnosis of cancer at the molecular level, and astonishing new treatments based on a patient’s own DNA. To make the remarkable promise of this new era a reality, we must make sure that patients can take DNA tests, free of the fear that their genetic information will somehow be used to discriminate against them. We took a major step toward unlocking the potential of this new era by approving strong protections against genetic discrimination in health insurance and employment when the Genetic Nondiscrimination Act was signed into law last year.

In sum, we need a new model for research, prevention and treatment of cancer, and we are here today to start that debate in Congress. We must move from a magic bullet approach to a broad mosaic of care, in which survivorship is also a key part of our approach to cancer. By doing so, we can take a giant step toward reducing or even eliminating the burden of cancer in our nation and the world. It’s no longer an impossible dream, but a real possibility for the future.

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Press Contact

Anthony Coley/ Melissa Wagoner (202) 224-2633

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Kennedy Renews the War Against Cancer

March 26, 2009

FOR IMMEDIATE RELEASE

Bill will Renew America’s Commitment to Fighting Cancer and Finding Cures

WASHINGTON, DC— Senators Edward M. Kennedy and Kay Bailey Hutchison today introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling this disease. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Kennedy.

The 21st Century Cancer ALERT Act will provide critical funding for promising research in early detection, and supply grants for screening and referrals for treatment. These measures will also ensure patient access to prevention and early detection, which is supplemented by increased access to clinical trials and information.

The bill places an emphasis on strengthening cancer research and the urgent need for resources to both prevent and detect cancers at an early stage. The bill strives to give scientists the tools they need to fight cancer and to understand more thoroughly how the disease works. Through fostering new treatments, increased preventative measures and funding for research, the ALERT Act begins a new chapter in how Americans will live with and fight cancer.

Senators Kennedy and Hutchison first proposed the idea for comprehensive cancer legislation last May, when the Health, Education, Labor and Pensions Committee held a hearing to discuss the need for a renewed focus on the deadly disease. Elizabeth Edwards, Lance Armstrong and Hala Moddelmog from Susan G. Komen for the Cure testified at the hearing.

Senator Kennedy, Chairman of the Health, Education, Labor, and Pensions Committee, said, “We’ve come a long way in fighting cancer since we passed the National Cancer Act thirty-eight years ago, but not far enough. Americans still live in fear that they or someone they love will be affected. Today, we’re better equipped for the fight— learning each and every day a little bit more about the disease and what we can do to fight it. Cancer is a complex disease and it requires comprehensive strategies to fight it— strategies that integrate research, prevention and treatment. This bill will renew our efforts to make progress in the battle against cancer, and to give patients and their families a renewed sense of hope.”

“Our nation declared the War on Cancer in 1971, yet, nearly 38 years later, cancer is expected to become the leading killer of Americans. We must bring renewed focus and vigor to this fight.” said Senator Hutchison. “The prescription isn’t simple, but there are steps we must take if we are going to see the cancer diagnosis rate decline, while raising the prognosis for survival among those who do have the disease. Our legislation will enact those necessary steps so we may see more progress and coordination in cancer research and treatment.”

“We know how to lengthen and improve the lives of people with cancer, but we’ve chosen as a nation to turn our backs on some of us who have the disease,” said Elizabeth Edwards. “I urge the United States Senate to embrace the ALERT Act and get it to the President’s desk as soon as possible.”

“In 2010, cancer is expected to be the leading cause of death worldwide. Every American is touched by this disease,” said Lance Armstrong, chairman and founder of the Lance Armstrong Foundation. “The 21st Century Cancer ALERT Act and its authors’ leadership in reforming our nation’s approach to the war on cancer are a very welcome step forward to every member of the LIVESTRONG movement.”

“It’s been 38 years since our nation first declared war on cancer, and yet we are still facing a significant cancer crisis.  The Kennedy-Hutchison Cancer ALERT Act will reignite the war on cancer,” said Nancy G. Brinker, founder of Susan G. Komen for the Cure.  “We must all work together and let nothing stand in the way of discovering and delivering the cures to cancer.”

Senate action on this bill is expected this Congressional session.

A section-by-section summary of the legislation is below as well as an op-ed authored by Senators Hutchison and Kennedy that appeared this morning in the Houston Chronicle and on the Boston Globe’s website.

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21^st Century Cancer ALERT Act

Senators Kennedy and Hutchison

Section by Section Summary

The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

Section 1 and 2 – Findings and Declaration of Purpose

Section 3- Advancement of the National Cancer Program (NCP)

Modernize the role of the National Cancer Institute (NCI) in coordinating the NCP

• Identifies relevant federal agencies to coordinate with NCI
• Improves the annual budget estimate for the NCP by including the needs of the entire NCP and submitting the budget annually to House and Senate Budget and Appropriations Committees
• Increases participation of other federal agencies in the National Cancer Advisory Board
• Encourages early detection and translational research opportunities

Biological Resource Coordination and Advancement of Technologies for Cancer Research

• Establishes an entity within NCI to support an interconnected network of biorepositories with consistent, interoperable systems for collection, storage, annotation, and information sharing
• Facilitates research by linking cancer registries to other federal data sources including those at Centers for Medicare and Medicaid Services [CMS], Social Security Administration, and Centers for Disease Control and Prevention
• Requires hospitals and ambulatory care centers that receive federal funds to offer patients the opportunity to contribute their biospecimens and clinical data to a clinical registry

Section 4 – Comprehensive and Responsible Access to Research, Data, and Outcomes

• Calls for guidance from the Office of Human Research Protection on the use of a centralized Institutional Review Board
• Improves privacy standards in clinical research by clarifying when de-identified patient information may be disclosed
• Calls for HHS to study the advantages and disadvantages of the synchronization of the standards for research under the Common Rule and the Privacy Rule
• Clarifies the application of the Privacy Rule to external researchers

Section 5- Enhanced Focus and Reporting on Cancer Research

• Calls for NCI to report annually on plans and progress regarding research on cancers with low incidence and low survival rates
• Establishes grants program to conduct research on cancers with low incidence and low survival rates

Section 6 – Continuing Access to Care for Prevention and Early Detection

Screening and Early Detection

• Establishes a grant program to states for colorectal cancer screening and referrals for medical treatment (similar to the national breast and cervical cancer early detection program). States are given the option to cover screened persons found to have cancer under Medicaid.

Cancer Prevention

• Authorizes grants for a medical mobile van program to conduct cancer screening and prevention education activities in communities that are underserved and suffer from barriers to preventative cancer care

Access to Prevention and Early Detection for Certain Cancers

• Calls for the Secretary to include cancers with especially low survival rates in the Cancer Genome Atlas Consortium
• Calls for the Secretary to establish formal working groups for cancers with especially low survival rates in the Early Detection Research Network
• Calls for the National Institute of Biomedical Imaging and Bioengineering to ensure that the Quantum Grant program and the Image Guided Interventions program expedite the development of interventions for cancers with low survival rates

Section 7– Early Recognition and Treatment of Cancer Through the Use of Biomarkers

Promote the Discovery and Development of Biomarkers

• Establishes and coordinates federal agencies to establish a highly directed, contract based program that will support the development of innovative biomarker discovery technologies
• Calls for FDA and CMS to work together to create guidelines for clinical study designs that will enable sponsors to generate clinical data that will be adequate for review by both agencies
• Conducts a demonstration project to provide limited regional coverage for biomarker tests and establish procedures for independent research entities to conduct high quality assessments of the efficacy and cost effectiveness of biomarker tests

Section 8: National Cancer Coverage Guidelines

Ensure Patient Access to Clinical Trials

• Facilitates expanded access to clinical trials by requiring ERISA governed health plans to continue to provide coverage of routine care regardless of whether a patient enrolls in a clinical trial

Section 9: Health Professions Workforce

Ensure a Stable Workforce for the Future

• Supports retired nurse military officers to work as nurse faculty
• Directs Secretary of Health and Human Services to identify oncology workforce gaps

Section 10: Patient Navigator Program

Improve Upon Existing Patient Navigator Programs

• Ensures that patient navigators meet minimum core proficiencies
• Reauthorizes the Patient Navigator program through 2015

Section 11: Cancer Care and Coverage Under Medicaid and Medicare

Improvements in Coverage of Cancer Services

• Codifies current Medicare policy to reimburse for routine care while patients are enrolled in clinical trials
• Conducts a demonstration project to evaluate the cost, effectiveness, and potential savings to Medicare of reimbursing providers for comprehensive cancer care planning services to the Medicare population
• Directs states to offer tobacco cessation medications and counseling to pregnant women enrolled in Medicaid

Section 12: Cancer Survivorship and Complete Recovery Initiatives

Childhood Cancers

• Establishes priority areas for NIH activities related to childhood cancer survivorship
• Authorizes grants for research on the causes of health disparities in childhood cancer survivorship and to evaluate follow up care for childhood cancer survivors

Complete Recovery Care

• Defines “complete recovery care” which includes care to address secondary effects of cancer and its treatment, including late and psychosocial effects
• Coordinates complete recovery care activities across federal agencies
• Establishes a Collaborative that will develop a plan for workforce development for complete recovery care

Section 13: Activities of the Food and Drug Administration

Sense of the Senate

• Encourages the FDA to harmonize policies to facilitate the development of drugs; explore clinical trial endpoints; and, modernize the Office of Oncology Drug Products

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Renewing the War on Cancer

By Edward M. Kennedy and Kay Bailey Hutchison

Kay Bailey Hutchison, U.S. Senator For State of Texas

Cancer is a relentless disease. It doesn’t discriminate between men and women, wealthy or poor, the elderly or the young. In 2008, over 1.4 million Americans were diagnosed with some form of the disease. If it wasn’t you, it may have been a spouse or sibling, a parent or a child, a friend or a coworker. We, too, have known the challenges of cancer diagnoses for ourselves or our family members or friends. And while there are many stories of survival, this disease still takes far too many lives. More than half a million Americans lost their battle with cancer last year.

Since the War on Cancer was declared in 1971, we have amassed a wealth of knowledge about the disease. Advances in basic and clinical research have improved treatments significantly. Some of the most important progress has been made in prevention and early detection, particularly screening, including mammography and colonoscopy. Behavior modifications, such as smoking cessation, better eating habits, regular exercise, and sunscreen have been found to prevent many cancers. Continued focus must be placed on prevention, which will always be the best cure.

Though heightened awareness and prevention should be emphasized, alone they don’t translate into adequate progress for those with cancer. Since 1971, the cancer mortality rate has decreased by only 6 percent. In the same period, by contrast, mortality rates have dramatically declined for heart disease (by 56 percent) and stroke (by 66 percent). Today, cancer is the second leading cause of death in the United States, exceeded only by heart disease. If the current trend continues, the National Cancer Institute predicts that one in every two men and one in every three women will be diagnosed with cancer in their lifetimes, and that cancer will become the leading killer of Americans.

The solution isn’t easy, but there are steps we should take now if we hope to see the diagnosis rate decline substantially and the survival rate increase.  To do so, we must identify and remove the numerous barriers that obstruct our progress in cancer research and treatment.

First, it is essential that cancer be diagnosed at an initial, curable stage. One of the most promising breakthroughs is the monitoring of biomarkers, which leave evidence within the body that alerts clinicians to hidden activity indicating that cancer may be developing. Identification of such biomarkers can lead to the earliest possible detection of cancer in patients.

Second, even if we significantly improve early detection, lack of health insurance and other impediments to care will preclude many Americans from undergoing routine screening. With early screening, the disease may be detected at a treatable stage and dramatically increase the rate of survival. Greater outreach is clearly needed to make screening more available to all, and especially to underserved populations.

Third, we must adopt a more coordinated approach to cancer research. Establishing an interconnected network of biorepositories with broadly accessible sources of tissue collection and storage will enable investigators to share information and samples much more effectively. Integrated research will help accelerate the progress of lifesaving research. The search for cures should also be a cooperative goal. The current culture of isolated career research must yield to more cooperative arrangements to expedite breakthroughs. Our national policy should encourage all stakeholders in the War on Cancer to become allies and work in concert toward cures.

Fourth, as our nation’s best and brightest researchers seek new ways to eradicate cancer, we must improve treatment for those who have it today. Raising awareness of clinical trials would result in more patients and their doctors knowing what promising trials are available. Doing so will expand treatment options for patients, and enable researchers to develop better methods for prevention, diagnosis, and therapy.  Today, less than five percent of the 10 million adults with cancer in the United States participate in clinical trials. Disincentives by the health insurance market, preventing patients from enrolling in clinical trials, must be eliminated.

Finally, as our knowledge of cancer advances and patients live longer, we need a process that will improve patient survivorship through comprehensive care planning services. There is great value in equipping patients with a treatment plan and summary of their care when they first enter remission, in order to achieve continuity of therapy and preventing costly, duplicative, or unnecessary services.

We have introduced bipartisan legislation to bring about these necessary changes, and we hope to see the bill enacted in the coming weeks and months. These policy initiatives cannot be fully implemented without broad support and sufficient resources, and we are committed to leading this effort to completion.

It’s time to reinvigorate the War on Cancer, and more effective coordination of policy and science is indispensible for rapid progress.