“Too Often We Underestimate The Power Of A Touch”*

One of the most comforting forms of support you can give a person with cancer is the use of touch. Family caregivers can significantly reduce symptoms in cancer patients at home through use of simple touch and massage techniques. These findings were recently reported at the 6th International Conference of the Society for Integrative Oncology.

Study Shows Family Caregivers’ Simple Touch Techniques Reduce Symptoms in Cancer Patients

One of the most comforting forms of support you can give a person with cancer is the use of touch.  Family caregivers can significantly reduce symptoms in cancer patients at home through use of simple touch and massage techniques. These findings were recently reported at the 6th International Conference of the Society for Integrative Oncology.

The study, sponsored by the National Cancer Institute, evaluated outcomes of a 78 minute DVD instructional program and illustrated manual in a sample of 97 patients and their caregivers. The multi-ethnic sample represented 21 types of cancer (nearly half with breast cancer) and all stages of disease. Caregivers included spouses, adult children, parents, siblings and friends. The project was conducted in Boston, Massachusetts, Portland, Maine, and Portland, Oregon using English, Spanish and Chinese languages.

“Too often we underestimate the power of a touch, a smile, a kind word, a listening ear, an honest compliment, or the smallest act of caring, all of which have the potential to turn a life around.”  — Leo F. Buscaglia, from his book entitled, Living, Loving & Learning.

William Collinge, Ph.D., MPH, President, Collinge and Associates. Dr. Collinge is a consultant, author, speaker and researcher in the field of integrative health care. He has served as a scientific review panelist for the National Institutes of Health in mind/body medicine, complementary therapies & health care services

According to the principal investigator, William Collinge, PhD, MPH, president of Collinge and Associates states, “Touch and massage are among the most effective forms of supportive care in cancer, but most patients cannot access professional practitioners of these methods on a regular basis. This study sought to determine whether family caregivers receiving brief home-based instruction could deliver some of the same benefits as professionals. It appears they can.”

In the study, couples were randomized to either an experimental group using the program, or an attention control group. Caregivers in the experimental group were asked to apply the instruction for at least 20 minutes, three or more times per week for a month. Those in the control group were assigned to read to the patient for the same amounts of time. Patients completed report cards before and after sessions rating their levels of pain, fatigue, stress/anxiety, nausea, depression, and other symptoms.

Results indicated significant reductions for all symptoms after both activities, indicating that companionship alone has a positive effect. However, while symptoms were reduced from 12-28% after reading, massage from the caregiver led to reductions of 29-44%. The greatest impact was on stress/anxiety (44% reduction), followed by pain (34%), fatigue (32%), depression (31%), and nausea (29%). Patients reporting an optional “other” symptom (e.g., headaches) saw reductions of 42% with massage. Caregivers in the massage group also showed gains in confidence and comfort with using touch and massage as forms of caregiving.

According to Collinge, “It appears that family members who receive simple instruction in safety and techniques can achieve some of the same results as professional practitioners. This has important implications not just for patient well-being, but for caregivers as well. Caregivers are at risk of distress themselves – they can feel helpless and frustrated when seeing a loved one suffer. This gives a way to make a difference for the patient, and at the same time increase their own satisfaction and effectiveness as a caregiver. It also appears to strengthen the relationship bond, which is important to both.”

The DVD program, titled Touch, Caring and Cancer: Simple Instruction for Family and Friends,  is expected to be released to the public during the week of November 22, 2009. The DVD program will be available in English, Spanish and Chinese. More information and video trailers are available at www.partnersinhealing.net.

Vodpod videos no longer available.

About Collinge and Associates

Collinge and Associates is an independent research and consulting organization based in Kittery, Maine. The group conducts research in complementary therapies for the National Institutes of Health, and does scientific review consulting for NIH and other organizations. Website: www.collinge.org.

Sources:

• Study Shows Family Caregivers’ Simple Touch Techniques Reduce Symptoms in Cancer Patients, News Release, PartnersInHealing.net, November 13, 2009.

• Collinge W, Kahn J, Walton T, Fletcher K. Randomized controlled trial of family caregiver use of massage as supportive cancer care following multimedia instruction. Journal of the Society for Integrative Oncology, 2009, in press. [PDF Document]

*Title Source:

The title was excerpted from the words of Leo F. Buscaglia that appear in his book Living, Loving & Learning. Buscaglia was a teacher in the Department of Special Education at the University of Southern California (USC) in the late 1960’s. During his tenure at USC, one of Buscaglia’s students committed suicide.  The incident had a great impact on Buscaglia and led him to establish a non-credit class titled, Love 1A. The class led to lectures and a manuscript loosely based on what was shared in those weekly classes. The manuscript led to the publication of a book entitled, LOVE:  What life is all about.  Shortly thereafter, Leo Buscaglia’s presentations were taped by the Public Broadcasting System (PBS) and shown on television.  The PBS television presentations touched the hearts of many television viewers.  Buscaglia is often referred to as the granddaddy of motivational speakers. During his lifetime, Buscaglia was a popular speaker on television talk shows and the lecture circuit.  There was one point in time when five of his books appeared simultaneously on The New York Times Best Sellers List.

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].

“Decisions Are Made By Those Who Show Up”*

Responding to a threat of a funding reduction to the Department of Defense’s Ovarian Cancer Research Program, during the last week of October the Ovarian Cancer National Alliance urged advocates to contact their Members of Congress to appeal to the Appropriations Defense Subcommittee to increase funding for the research program. As a result of the Ovarian Cancer National Alliance’s advocacy efforts, 14 Senators and 77 Representatives showed their opposition to the funding cut by signing a Dear Colleague letter sent to the Subcommittee Tuesday, November 3, 2009. …

Advocates Work To Prevent Slash In Ovarian Cancer Research Funding

Responding to a threat of a funding reduction to the Department of Defense’s Ovarian Cancer Research Program, during the last week of October the Ovarian Cancer National Alliance (OCNA) urged advocates to contact their Members of Congress to appeal to the Appropriations Defense Subcommittee to increase funding for the research program.

Advocates lobbying on Capitol Hill for increased funds for ovarian cancer research. (Photo: Ovarian Cancer National Alliance)

As a result of OCNA’s advocacy efforts, 14 Senators and 77 Representatives showed their opposition to the funding cut by signing a Dear Colleague letter sent to the Subcommittee Tuesday, November 3, 2009.

The Dear Colleague letter, written by Senator Robert Menendez (D-NJ) and Congresswoman Rosa DeLauro (D-CT), requested that the Subcommittee allocate the $25 million set forth in the U.S. House of Representatives‘ version of the Defense bill, and not the $10 million outlined in the U.S. Senate version of the bill. The Senate funding level represented a 50 percent reduction from the $20 million appropriated in fiscal year (FY) 2009.

The date of the conference subcommittee meeting has yet to be announced.

Established in 1997, the Department of Defense’s Ovarian Cancer Research Program has received $10 million in funding annually from FY 1998 until FY 2008. However, for FY 2009, the program’s funding was doubled to $20 million. The Ovarian Cancer Research Program works to eliminate ovarian cancer by conducting innovative, multidisciplinary research on early detection, screening and treatment of ovarian cancer.

To read the full text of the letter and see if your elected officials signed, please click here.

The Ovarian Cancer Action Network periodically sends out action alerts to notify advocates of pressing issues that need constituent support. To sign up, please click here.

About the Ovarian Cancer National Alliance

OCNA is the advocacy arm of the ovarian cancer movement. OCNA works with federal policy makers, including the  U.S. President, U.S. Congress, and federal agencies like the U.S. Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS). OCNA commits its resources to be a voice for ovarian cancer survivors and significantly reduce the number of deaths from this deadly disease by advocating at the federal level for the following:

• Adequate and sustained funding for ovarian cancer research and awareness programs, and

• Legislation that improves quality of life and access to care for ovarian cancer patients.

Since 1997, when OCNA was founded, death rates from ovarian cancer have not significantly changed. However, OCNA has worked to increase funding for ovarian cancer research, with the goal that this funding will support breakthroughs to help detect ovarian cancer early, treat it more thoroughly, and allow women with ovarian cancer to survive, and thrive.

OCNA has worked to ensure that (i) necessary treatments are covered by Medicare, (ii) drugs and tests on the market are safe and effective, and (iii) federal policy makers are aware of the importance of the ovarian cancer community.

Join OCNA to fight for women with ovarian cancer, and policies that help support them and their families.

Source: Advocates Work To Prevent Slash In Ovarian Cancer Research Funding, News Update, Ovarian Cancer National Alliance, November 11, 2009.

*Title Quote:  Fictional U.S. President Josiah Edward Bartlet, What Kind of Day Has It Been Episode, The West Wing, created by Aaron Sorkin, originally aired May 17, 2000 [Sorkin attributes his teleplay quote to Woody Allen (“80% of success in life is just showing up”)].

Nationwide Registry to “Match” Study Volunteers With Researchers

Individuals who want to participate in research studies can connect online with researchers nationwide through the first disease-neutral, volunteer recruitment registry.  ResearchMatch.org is a not-for-profit secure Web site, designed to provide people who are interested in participating in research the opportunity to be matched with studies that may be the right fit for them.

NIH Announces First National Research Study Recruitment Registry

Nationwide Registry to “Match” Volunteers with Researchers

Barbara Alving, M.D., Director, National Center For Research Resources. "ResearchMatch is a tool that can improve the connection and communication between potential participants and researchers providing opportunities for the public to contribute to advancing new treatments."

Individuals who want to participate in research studies now can connect online with researchers nationwide through the first disease-neutral, volunteer recruitment registry.

ResearchMatch.org is a not-for-profit secure Web site, designed to provide people who are interested in participating in research the opportunity to be matched with studies that may be the right fit for them.

ResearchMatch offers an easy-to-use, free and safe way for volunteers to connect with thousands of researchers who are conducting research on a wide range of diseases.

The site is a collaborative effort of the national network of medical research institutions affiliated with the Clinical and Translational Science Awards (CTSAs). The CTSA program, which is led by the National Center for Research Resources (NCRR), a part of the National Institutes of Health, is focused on enhancing local and national efforts to enhance the translation of laboratory discoveries into treatments for patients.

“‘Participant recruitment continues to be a significant barrier to the completion of research studies nationwide — recent NIH data indicates that just 4 percent of the U.S. population has participated in clinical trials,’ said NCRR Director Barbara Alving, M.D.”

“Participant recruitment continues to be a significant barrier to the completion of research studies nationwide — recent NIH data indicates that just 4 percent of the U.S. population has participated in clinical trials,” said NCRR Director Barbara Alving, M.D. “ResearchMatch is a tool that can improve the connection and communication between potential participants and researchers providing opportunities for the public to contribute to advancing new treatments.”

” …One key difference is that ResearchMatch places the burden of connecting the right volunteers with the right study on the researchers, whereas Clinicaltrials.gov asks volunteers to identify the trials that could work for them. …”

The convenient and user-friendly registry employs a familiar research matching model that is complementary to Clinicaltrials.gov. One key difference is that ResearchMatch places the burden of connecting the right volunteers with the right study on the researchers, whereas Clinicaltrials.gov asks volunteers to identify the trials that could work for them.

“NIH data indicates that 85 percent of trials don’t finish on time due to low patient participation, and 30 percent of trial sites fail to enroll even a single patient. We aim to help combat these challenges with ResearchMatch.” — Gordeon Bernard, M.D., principal investigator of the Vanderbilt University CTSA

“ResearchMatch offers a convenient solution to the complex, competitive and often costly participant recruitment system,” said Gordon Bernard, M.D., principal investigator of the Vanderbilt CTSA, which hosts the national registry. “NIH data indicates that 85 percent of trials don’t finish on time due to low patient participation, and 30 percent of trial sites fail to enroll even a single patient. We aim to help combat these challenges with ResearchMatch.”

How ResearchMatch Works

ResearchMatch will match any interested individual residing in the United States with researchers who are approved to recruit potential research volunteers through the system. After an individual has self-registered to become a volunteer, researchMatch’s security features ensure that personal information is protected until volunteers authorize the release of their contact information to a specific study that may be of interest to them. Volunteers are notified electronically when they are a possible match and then make the decision regarding the release of their contact information. It also will promote choice as there are no obligations on the volunteer to participate in studies.

For the first year of the project, only researchers affiliated with participating CTSA institutions are eligible to use researchMatch. However, plans are in place to make researchMatch available beyond the CTSA consortium by 2011. Currently 52 individual institutions associated with 40 CTSA sites are part of the ResearchMatch network. A list of these institutions may be viewed here (http://ncrr.nih.gov/clinical_research_resources/clinical_and_translational_science_awards/researchmatch).

To learn more about researchMatch and to register as a volunteer, visit: www.researchmatch.org.

About the CTSA Consortium

The CTSA consortium is a national network of 46 medical research institutions working together to improve the way biomedical research is conducted across the country. The consortium, funded through Clinical and Translational Science Awards (CTSAs), shares a common vision to reduce the time it takes for laboratory discoveries to become treatments for patients and to engage communities in clinical research efforts. It also is fulfilling the critical need to train a new generation of clinical researchers. The CTSA program is led by the National Center for Research Resources, part of National Institutes of Health.

Launched in 2006, this network now includes awardees in 26 states. When the program is fully implemented, it will support approximately 60 CTSAs across the nation.

For more information about the CTSA program, visit www.ncrr.nih.gov/ctsa. The CTSA consortium Web site, which provides information on the consortium, current members and new grantees, can be accessed at www.CTSAweb.org.

About the National Center For Research Resources

The National Center for Research Resources, part of NIH, provides laboratory scientists and clinical researchers with the resources and training they need to understand, detect, treat and prevent a wide range of diseases. NCRR supports all aspects of translational and clinical research, connecting researchers, patients and communities across the nation. For more information, visit www.ncrr.nih.gov.

About the National Institutes of Health

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Source:  NIH Announces First National Research Study Recruitment Registry – Nationwide Registry to “Match” Volunteers with Researchers, NIH News, U.S. National Institutes of Health, U.S. Department of Health & Human Services, November 10, 2009.

UCLA Researchers Significantly Inhibit Growth of Ovarian Cancer Cell Lines With FDA-Approved Leukemia Drug Dasatinib (Sprycel®)

The drug dasatinib (Sprycel®), approved for use by the U.S. Food and Drug Administration in patients with specific types of leukemia, significantly inhibited the growth and invasiveness of ovarian cancer cells and also promoted their death, say UCLA researchers in the November 10th issue of the British Journal of Cancer. The drug, when paired with a chemotherapy regimen, was even more effective in fighting ovarian cancer cell lines in which signaling of the Src family kinases — associated with approximately one-third of ovarian cancers– is activated. Clinical trials that involve the testing of dasatinib against ovarian cancer and solid tumors are currently ongoing.

Researchers affiliated with the University of California, Los Angeles (UCLA), Mayo Clinic and Harvard Medical School announced that they have established a biological rationale to support the clinical study of the U.S. Food & Drug Administration (FDA)-approved leukemia drug dasatinib (U.S. brand name: Sprycel®), either alone or in combination with chemotherapy, in patients with ovarian cancer. The study appears in the November 10th edition of the British Journal of Cancer.

Background

Dasatinib is an FDA-approved drug for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). Dasatinib is a small-molecule inhibitor that targets several tyrosine kinases, including the Src kinase family, Ephrin type-A receptor 2 ( EphA2) , and the focal adhesion kinase (FAK).

Src is the prototypic member of a family of nine non-receptor tyrosine kinases (Src, Lyn, Fyn, Lck, Hck, Fgr, Blk, Yrk, and Yes). The Src family kinase (SFK) proteins regulate four main cellular fuctions that ultimately control the behavior of transformed cancer cells:  cell proliferation, adhesion, invasion, and motility.

Eph receptors and ephrins are integral players in cancer formation and progression, and are associated with advanced ovarian cancer and poor clinical outcome.

FAK is a non-receptor tyrosine kinase involved in the regulation of cell adhesion, survival, and migration.  Preclinical studies indicate that FAK plays a signficant role in ovarian cancer cell migration and invasion.

Dasatinib Study Methodology & Findings

One of the dasatinib study authors is Dennis J. Slamon, M.D. Ph.D. Dr. Slamon is the Director of Clinical/Translational Research & Director of the Revlon/UCLA Women's Cancer Research Program, at the UCLA Jonsson Comprehensive Cancer Center. He is also the co-discoverer of Herceptin®, a targeted therapy that revolutionized the treatment of HER-2 positive breast cancer.

The researchers carried out the study by testing the effects of dasatinib on human ovarian cancer cells in vitro, using a panel of 34 established human ovarian cancer cell lines.  The 34 cell lines selected were representative of the major epithelial ovarian cancer subtypes:

• 18 cell lines were obtained from patients with serous papillary ovarian cancer;

• 8 cell lines were obtained from patients with clear cell ovarian cancer;

• 4 cell lines were obtained from patients with undifferentiated ovarian cancer; and

• 4 cell lines were obtained from patients with endometrioid or mucinous ovarian cancer.

On this basis, the researchers examined the effects of dasatinib on ovarian tumor cell proliferation, invasion, apoptosis, and cell-cycle arrest.  To more fully understand the activity of dasatinib, the researchers also studied the efficacy of chemotherapeutic drugs (i.e., carboplatin and paclitaxel) in combination with dasatinib against ovarian cancer cells that were previously determined to be dasatinib-sensitive.

The overarching goals of the study were (i) to provide a rationale to test dasatinib as a single agent or in combination with chemotherapy in patients with ovarian cancer, and (ii) to identify molecular markers that may help define subsets of ovarian cancer patients most likely to benefit from treatment with dasatinib.

Significant findings reported in the dasatinib study are summarized below.

• Concentration-dependent, anti-proliferative effects of dasatinib were seen in all ovarian cancer cell lines tested.

• Dasatinib significantly inhibited tumor cell invasion, and induced tumor cell death, but was less effective in causing tumor cell-cycle arrest.

• At a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for dasatinib plus carboplatin or paclitaxel.

• 24 out of 34 (71%) representative ovarian cancer cell lines were highly sensitive (i.e.,  ≥ 60% growth inhibition) to dasatinib.

• 6 cells lines were moderately sensitive (i.e., 40% – 59% growth inhibition) to dasatinib.

• 4 cell lines were resistant (i.e., < 40% growth inhibition) to dasatinib.

• When comparing dasatinib sensitivity between cell lines based solely upon histological subtype (i.e., serous papillary, clear cell, endometrioid, mucinous, and undifferentiated ovarian cancer cell lines), no single histological subtype was more sensitive than another.

• Ovarian cancer cell lines with high expression of Yes, Lyn, Eph2A, caveolin-1 and 2, moesin, annexin-1 and 2 and uPA (urokinase-type Plasminogen Activator), as well as those with low expression of IGFBP2 (insulin-like growth factor binding protein 2), were particularly sensitive to dasatinib.

• Ovarian cancer cell lines with high expression of HER-2 (Human Epidermal growth factor Receptor 2), VEGF (Vascular endothelial growth factor) and STAT3 (Signal Transducer and Activator of Transcription 3) were correlated with in vitro resistance to dasatinib.

Based upon the findings above, the researchers concluded that there is a clear biological rationale to support the clinical study of dasatinib, as a single agent or in combination with chemotherapy, in patients with ovarian cancer.

Gottfried E. Konecny, M.D., UCLA Assistant Professor of Hematology/Oncology, UCLA Jonsson Comprehensive Cancer Center Researcher & First Author of the Dasatinib Study

Ovarian cancer, which will strike 21,600 women this year and kill 15,500, causes more deaths than any other cancer of the female reproductive system. Few effective therapies for ovarian cancer exist, so it would be advantageous for patients if a new drug could be found that fights the cancer, said Gottfried E. Konecny, M.D., a UCLA assistant professor of hematology/oncology, a Jonsson Comprehensive Cancer Center researcher, and first author of the study.

“I think Sprycel® could be a potential additional drug for treating patients with Src dependent ovarian cancer,” Konecny said. “It is important to remember that this work is only on cancer cell lines, but it is significant enough that it should be used to justify clinical trials to confirm that women with this type of ovarian cancer could benefit.”

Recent gene expression studies have shown that approximately one-third of women have ovarian cancers with activated Src pathways, so the drug could potentially help 7,000 ovarian cancer patients every year. Notably, a gene expression study published in 2007 reported Src activation in approximately 50% of the ovarian cancer tumors examined.

In the dasatinib study, the UCLA team tested the drug against 34 ovarian cancer cell lines and conducted genetic analysis of those lines. Through these actions, the researchers were able to identify genes that predict response to dasatinib. If the work is confirmed in human studies, it may be possible to test patients for Src activation and select those who would respond prior to treatment, thereby personalizing their care.

“We were able to identify markers in the pre-clinical setting that would allow us to predict response to Sprycel®,” Konecny said. “These may help us in future clinical trials in selecting patients for studies of the drug.”

Dasatinib is referred to as a “dirty” kinase inhibitor, meaning it inhibits more than one cellular pathway. Konecny said it also inhibits the focal adhesion kinase (FAK) and ephrin receptor, also associated with ovarian cancer, in addition to the Src cellular pathway.

The next step, Konecny said, would be to test the drug on women with ovarian cancer in a clinical trial. The tissue of responders would then be analyzed to determine if the Src and other pathways were activated. If that is confirmed, it would further prove that dasatinib could be used to fight ovarian cancer. In studies, women would be screened before entering a trial and only those with Src dependent cancers could be enrolled to provide further evidence, Konecny said, much like the studies of the molecularly targeted breast cancer drug Herceptin® enrolled only women who had HER-2 positive disease.

“Herceptin® is different because we knew in advance that it only worked in women with HER-2 [gene] amplification,” he said. “In this case, we don’t clearly know that yet. The data reassures us that the drug works where the targets are over-expressed but we need more testing to confirm this.”

The tests combining the drug with chemotherapy are significant because chemotherapy, namely carboplatin and paclitaxel, is considered the standard first line treatment for ovarian cancer patients following surgery. Because dasatinib proved to have a synergistic effect when combined with chemotherapy, it may be possible to add this targeted therapy as a first line treatment if its efficacy is confirmed in future studies.

Dasatinib Study Significance

The dasatinib study is potentially significant to the area of ovarian cancer treatment for several reasons.

First, although this study only tested dasatinib in vitro against ovarian cancer cell lines, the drug is already FDA-approved.  Accordingly, the general safety of the drug has already been established by the FDA.

Second, 71% of the ovarian cancer lines were highly sensitive to dasatinib.

Third, dasatinib was additive to, or synergistic with, the standard of care chemotherapy drugs used in first line ovarian cancer treatment, i.e., carboplatin and paclitaxel.

Fourth, the study established molecular markers that may be predictive of dasatinib effectiveness in particular patients.  In theory, a patient’s tumor biopsy could be tested for the presence of those molecular markers to determine whether a patient will benefit from dasatinib.

Fifth, one of the dasatinib study authors is Dennis J. Slamon, M.D. Ph.D. Dr. Slamon is the director of Clinical/Translational Research, and director of the Revlon/UCLA Women’s Cancer Research Program, at the UCLA Jonsson Comprehensive Cancer Center. Dr. Slamon is also the co-discoverer of Herceptin®, a targeted therapy that revolutionized the treatment of HER-2 positive breast cancer.  Herceptin® is a targeted therapy that kills HER-2 positive breast cancer cells while leaving normal cells unaffected.  The potential use of dasatinib to treat select ovarian cancer patients who test “positive” for specific molecular markers (e.g., Src cellular pathway activation) is similar to the extremely successful drug development approach used for Herceptin®.

Open Clinical Trials Testing Dasatinib (Sprycel®) Against Ovarian Cancer & Solid Tumors

As of this writing, there are several open (i.e., recruiting) clinical trials that involve testing dasatinib against ovarian cancer and solid tumors.

For a list of open clinical trials that involve testing dasatinib against ovarian cancer, CLICK HERE.

For a list of open clinical trials that involve testing dasatinib against solid tumors, CLICK HERE.

All potential volunteers must satisfy the clinical trial entrance criteria prior to enrollment.  Depending on the drug combination being tested, one or more of the solid tumor clinical trials may not be appropriate for an ovarian cancer patient.

About the UCLA Jonsson Comprehensive Cancer Center

UCLA’s Jonsson Comprehensive Cancer Center (JCCC) has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, JCCC is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2009, JCCC was named among the top 12 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 consecutive years. For more information on JCCC, visit the website at http://www.cancer.ucla.edu.

Sources:

• Konecny GE, Glas R, Dering J,et. al. Activity of the multikinase inhibitor dasatinib against ovarian cancer cells. Br J Cancer. 2009 Oct 27. [Epub ahead of print, doi:10.1038/sj.bjc.6605381.] PubMed PMID: 19861960. [Full Study Text PDF Document]

• FDA Approved Leukemia Drug Shows Promising Activity in Ovarian Cancer Cell Lines, Press Release, In the News, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, November 10, 2009

• Dressman HK, Berchuck A, Chan G, et. al. An integrated genomic-based approach to individualized treatment of patients with advanced-stage ovarian cancer. J Clin Oncol. 2007 Feb 10;25(5):517-25. PubMed PMID: 17290060.

• Baggerly KA, Coombes KR, Neeley ES. Run batch effects potentially compromise the usefulness of genomic signatures for ovarian cancer. J Clin Oncol. 2008 Mar 1;26(7):1186-7.

• Dressman HK, Lancaster J, Nevins JR, Potti A. In Reply, Correpondence. J Clin Oncol. 2008 Mar 1;26(7):1187-8.

Æterna Zentaris’ LHRH-Receptor Targeted Therapy AEZS-108 Produces Positive Preliminary Results in Advanced Stage Ovarian Cancer

Preliminary Phase II clinical study evaluation shows that primary efficacy endpoint has been met for patients with advanced-stage, platinum-resistant, taxane-pretreated ovarian cancer who were treated with the targeted therapy AEZS-108.

Æterna Zentaris Inc. , a global biopharmaceutical company focused on endocrine therapy and oncology, today announced positive efficacy data from a Phase II study with its targeted therapy AEZS-108 (formerly AN-152 or ZEN-008), in patients with platinum–resistant, taxane-pretreated ovarian cancer. In a personalized healthcare approach, the study selected patients with tumors expressing luteinizing hormone-releasing hormone (LHRH) receptors, the key element in the targeting mechanism of AEZS-108. Under coordination by Prof. Günter Emons, MD, Chairman of the Department of Obstetrics & Gynaecology at the University of Göttingen, Germany, this open-label, multi-center and multi-national Phase II study (AGO-GYN 5) is being conducted by the German AGO Study Group (Arbeitsgemeinschaft Gynäkologische Onkologie / Gynaecological Oncology Working Group; www.ago-ovar.de), in cooperation with clinical sites in Europe.

Preliminary Phase II Clinical Study Results

Juergen Engel, Ph.D., President & Chief Executive Officer, Æterna Zentaris Inc. (Photo: AEterna Zentaris Inc.)

All 43 patients with LHRH-receptor positive ovarian cancer who entered study AGO-GYN 5 have completed their study treatment. A preliminary evaluation shows that the study met its primary efficacy endpoint of 5 or more responders in 41 evaluable patients.

Responders, as well as patients with stable disease after completion of treatment with AEZS 108, will now be followed to assess the duration of progression-free survival and, ultimately, overall survival. More detailed analyses, which will also include efficacy data from post-treatment follow-up of the ovarian cancer patients, are currently in preparation and will be presented at forthcoming scientific conferences.

Juergen Engel, Ph.D., Æterna Zentaris President and Chief Executive Officer stated, “We are pleased with the progress of this project. The successful completion of the recruitment and treatment phase and the apparent activity in this difficult group of cancer patients is encouraging. This is the basis we were looking for, in order to take the next steps in the further development of AEZS 108 in gynecological cancers and possibly also in prostate cancer.”

About the AEZS-108 Phase II Clinical Study

AEZS-108 represents a new targeting concept in oncology using a cytotoxic peptide conjugate which is a hybrid molecule composed of a synthetic peptide carrier and a well-known cytotoxic agent, doxorubicin. The design of this product allows for the specific binding and selective uptake of the cytotoxic conjugate by LHRH-receptor-positive tumors. The binding of AEZS-108 to cancerous cells that express these receptors results in its accumulation and preferential uptake in the malignant tissue.

In a Phase II study program entitled, “The antitumoral activity and safety of AEZS 108 (AN 152), a LHRH agonist linked doxorubicin in women with LHRH-receptor positive gynecological tumors“, patients with tumors expressing LHRH receptors are administered an intravenous infusion of 267 mg/m2 of AEZS 108 over a period of 2 hours, every Day 1 of a 21-day (3-week) cycle. The proposed duration of the study treatment is 6, 3-week cycles. Study AGO GYN 5 is performed with 14 centers of the German Gynecological Oncology Working Group (AGO; www.ago-ovar.de), in cooperation with 3 clinical sites in Europe.

The program was designed to include up to 82 patients; approximately 41 with a diagnosis of platinum-resistant, taxane-pretreated ovarian cancer, and 41 with disseminated endometrial cancer. For both indications, patient recruitment was planned in 2 stages with 21 and 20 patients, respectively, and the primary efficacy endpoint at the end of stage 2 was defined as 5 or more patients with partial or complete tumor responses according to Response Evaluation Criteria in Solid Tumors (RECIST) and/or Gynecologic Cancer Intergroup (GCIG) guidelines. Secondary endpoints include time to progression, survival, toxicity, as well as adverse effects.

Prior Phase I Clinical Trial Results

On June 3, 2007 positive results of an open, multi-center, sequential group, dose-escalation Phase I study in various gynecological cancers were presented at the American Society of Clinical Oncology’s (ASCO) Annual Meeting in Chicago, Illinois. Seventeen (17) patients with LHRH-receptor positive gynecological cancers were recruited. AEZS-108 was administered by intravenous infusion over two hours at dosages of 10, 20, 40, 80,160 and 267 mg/m2. At 160 mg/m2, six patients had a total of 32 cycles and at 267 mg/m2, seven patients had a total of 27 cycles. Most of the patients had been pretreated with various chemotherapies.

The study showed that AEZS-108 was well tolerated by patients with gynecological tumors. Furthermore, AEZS-108 is the first drug in a clinical study that targets the cytotoxic activity of doxorubicin specifically to LHRH-receptor expressing tumors. Finally, signs of anti-tumor activity were observed in seven out of 13 patients treated with 160 or 267 mg/m2 of AEZS 108, including three patients with complete or partial response

About AEZS-108

AEZS-108 Mechanism of Action (Photo: AEterna Zentaris Inc.)

AEZS-108 is a targeted cytotoxic peptide conjugate which is a hybrid molecule composed of a synthetic peptide carrier and a well-known cytotoxic agent, doxorubicin. The design of this product allows for the specific binding and selective uptake of the cytotoxic conjugate by LHRH-receptor-positive tumors. The binding of AEZS-108 to cancerous cells that express these receptors results in its accumulation in the malignant tissue. This binding is followed by internalization and retention of the cytotoxic drug, doxorubicin, in the cells. Therefore, since they target specific cells, cytotoxic conjugates are postulated to be less toxic, have less side-effects and are more effective in vivo than the respective non-conjugated/non-linked cytotoxic agents in inhibiting tumor growth.

About Ovarian and Endometrial Cancer

Ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women, with most of the cases occurring in women between 50 and 75 years of age. Overall, ovarian cancer accounts for 4% of all cancer diagnoses in women and 5% of all cancer deaths. Approximately 26,000 new cases and 17,000 deaths from this disease are estimated in the European community every year (Source: Gynecologic Oncology, Volume 92, Issue 3, March 2004, Pages 819-826).

Cancer of the endometrium is the most common gynecologic malignancy and accounts for 6% of all cancers in women. The majority of the cases occur in postmenopausal women, with the largest number of women developing their cancers during their sixth decade. Approximately 38,000 new cases and 9,000 deaths from this disease are estimated annually in Europe (Source: Annals of Oncology 15:1149-1150, 2004).

About Æterna Zentaris Inc.

Æterna Zentaris Inc. is a global biopharmaceutical company focused on endocrine therapy and oncology, with proven expertise in drug discovery, development and commercialization. News releases and additional information are available at www.aezsinc.com.

Sources:

• Æterna Zentaris Announces Positive Preliminary Results for Phase 2 Study with LHRH-Receptor Targeted Cytotoxic Conjugate AEZS 108 in Ovarian Cancer, Press Release, AEterna Zentaris Inc., November 2, 2009.

• Antitumoral Activity and Safety of AEZS-108 (AN-152), a LHRH Agonist Linked Doxorubicin, in Women With LHRH Receptor Positive Gynecological Tumors, Clinical Trial Protocol Summary, ClinicalTrials.gov (ID: NCT00569257), U.S. National Institutes of Health, August 2009.

• Emons G, Kaufmann M, Günthert A, et. al. Phase I study of ZEN-008 (AN-152), a targeted cytotoxic LHRH analog, in female patients with cancers expressing LHRH receptors. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: Abstr.#3571.

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.