Ovarian cancer is the most deadly cancer of the female reproductive system. It is estimated that this cancer alone will claim 15,460 American women's lives in 2011. Often known as "the silent killer," ovarian cancer is difficult to detect early because the ovaries are deep within the pelvis and initial symptoms are often ambiguous. Too often the cancer goes undiagnosed until after the disease is far advanced and has spread throughout the abdomen or to distant organs. After the cancer has metastasized, survival rates plummet because the current treatments are largely ineffective in fighting late stage ovarian cancer. More effective treatments and better early detection tools must be developed to meet the unmet needs of ovarian cancer patients and save their lives.

The National Foundation for Cancer Research funds an array of research projects conducted by leading scientists in the field of ovarian cancer research. Through their innovative and diversified approaches to developing new models for ovarian cancer treatment; finding ways to enhance the treatment efficacy of standard chemotherapy; discovering and developing gene therapies that suppress tumor metastasis; and collecting and annotating precious ovarian tumor tissues for developing early detection tools, these NFCR-funded scientists are gaining momentum in the battle against the most deadly gynecologic cancer of our time. Listed below are some notable ovarian cancer research programs that NFCR currently supports.

TARGETING OVARIAN CANCER

Breakthrough Discoveries of New Targets for Treating Ovarian Cancer
Robert C. Bast, Jr., M.D., University of Texas MD Anderson Cancer Center

Only about half of women with ovarian cancer will respond to the standard chemotherapy agent, paclitaxel, which is better known by its brand name, Taxol®. World renowned ovarian cancer researcher and NFCR scientist, Dr. Robert C. Bast, Jr., and his team at MD Anderson Cancer Center are conducting cutting-edge siRNA experiments to identify proteins in cancer cells that may regulate sensitivity to Taxol.

SiRNAs are strands of genetic material involved in decoding DNA instructions and reducing production of particular proteins in the cell. By testing a collection of siRNA molecules on ovarian cancer cell lines, the team has identified 14 siRNAs that alter the cancer cell's sensitivity to Taxol. These candidates can now be tested individually and in combination to determine whether reducing production of multiple proteins through the action of siRNA in tumor cells can further enhance tumor sensitivity to Taxol. When the optimal combinations have been identified in ovarian cancer cell lines, siRNAs and Taxol can be utilized in a new tumor model developed in the Bast lab. Because of the similarities between this powerful model and the actual disease in humans, new therapeutics can be rapidly moved into clinical trials to treat ovarian cancer patients. If Dr. Bast's approach is successful, the rate of response to Taxol and the survival of ovarian cancer patients will improve, giving them renewed hope of conquering their disease.

NFCR is Fighting Ovarian Cancer on a Global Scale
NFCR-Tianjin Cancer Institute Joint Tissue Banking Facility in Tianjin, China.

High quality cancer tissues and blood samples obtained directly from actual cancer patients are a most valuable resource for cancer researchers. From these specimens, scientists can extract DNA, RNA, and protein data to discover and analyze the underpinning molecular abnormalities of cancer. In 2004, NFCR and its partner in China established a cancer tissue bank that systematically collects human cancer tissues, blood, and other biospecimens, and preserves these precious samples for cancer research. To date, the tissue bank has collected and systematically annotated over 26,000 cancer tissues and nearly 16,000 blood samples, including about 450 ovarian tumor specimens and more than 200 blood samples from ovarian cancer patients. These samples are well preserved to keep them suitable for research with all the cutting-edge molecular techniques (such as DNA chip technology) for identifying new cancer biomarkers for early detection and molecular targets for drug development. This international research facility is currently partnering with two major pharmaceutical companies, Amgen and Pfizer, to develop early diagnostic tests and more effective targeted cancer therapies. Further growth of the tissue bank will continue to promote collaborative efforts on molecular cancer research for producing new life-saving treatments and diagnostic tools for patients around the world.

Making Taxol Work More Effectively
Susan Band Horwitz, Ph.D., Albert Einstein College of Medicine

Internationally renowned for her discovery of the molecular mechanism of Taxol, NFCR scientist Susan Band Horwitz, Ph.D., at the Albert Einstein College of Medicine in the Bronx continues her quest to explore why tumor resistance to Taxol occurs and how to make the drug work better. Dr. Horwitz reasons that during chemotherapy treatment, tumor cells may activate a protective molecular pathway which renders tumors resistant to Taxol. Her team may have found one such molecule - a growth factor that promotes cell survival called Insulin growth factor 2 or IGF2. When the researchers added an inhibitor of IGF2 in Taxol-resistant ovarian cancer cell lines, the cancer cells became sensitive again to the chemotherapy agent. Moreover, the Horwitz team is the first to evaluate the significance of IGF2 protein level in patients' tumors. She discovered that patients with high levels of IFG2 in their tumors had worse outcomes and a shortened time for their cancer to reoccur compared to those with low levels of IGF2. With continued success in this promising research, the targeted therapies which inhibit the IGF2 pathway that are now in clinical trials to treat other diseases may be considered as candidates to overcome Taxol resistance in ovarian cancer patients.

Recently, Dr. Horwitz was awarded the Lifetime Achievement Award by the American Association of Cancer Research. NFCR has been funding Dr. Susan Horwitz's research program for ten years and we applaud her for her continuing quest to find treatments that will overcome the resistance to Taxol, the agent that she knows so well and which has been used to treat over 1 million breast, ovarian, and lung cancer patients.

Stopping Cancer's Lethal Spread
NFCR Center of Metastasis Research, University of Kansas Cancer Center, Kansas City, KS
Center Director: Danny Welch, Ph.D.

Two-thirds of ovarian cancer cases are diagnosed when the disease has already spread throughout the abdomen and colonized in distant organs, and only 30% of women with late stage ovarian cancer survive five years or longer. Very little is known about how cancer cells spread to distant sites in the body and many researchers have shied away from the complex biology of metastatic cancer. But not those at the NFCR Center for Metastatic Research. Led by Danny Welch, Ph.D., this Center garners top researchers from universities across the United States to fulfill its quest - uncovering the complex biology of metastatic cancer. To date, the Center has discovered six metastasis suppressor genes in various types of cancer, and two of them - KISS1 and BRMS1 - are found in metastatic ovarian cancer. A key question to answer is how the protein products of these genes function to keep cancer cells from spreading. Dr. Welch's team has demonstrated that small KISS1 proteins called kisspeptins have metastasis suppression capabilities. They are now identifying cellular proteins that interact with kisspeptins, an important next step to reveal how kisspeptins mediate suppression of metastasis. Once the scientists know the partners of kisspeptins, they can design molecules that mimic them, leading to the development of novel anti-cancer therapies that prevent metastasis from happening or keep it dormant. If this can be achieved, it could bring ovarian cancer under control and give patients more hope for a cure and a longer life.

Striving to Escalate Support for Research on Early Detection of Ovarian Cancer
Robert C. Bast, Jr., M.D., University of Texas MD Anderson Cancer Center

Earlier is better, and for ovarian cancer, this is especially true. Until now, there hasn't been a reliable test available for early detection of ovarian cancer so only 19% of all cases are detected at an early, more treatable stage. A great deal of research is needed to discover new and more reliable biomarkers as an essential "next step" in improving early detection of this disease. It is our sincere hope that, with additional funding, NFCR will be able to expand support for research in this important area.

NFCR Project Director Robert C. Bast, Jr., M.D., is a world leader in the field of ovarian cancer early detection. In 1981, Dr. Bast discovered CA125, currently the most accurate marker for detecting early signs of ovarian cancer in the blood. In addition to his notable work, supported by NFCR, on developing more effective treatment for chemotherapy- resistant ovarian cancer, Dr. Bast and his research team continue to work on CA125 and other potential biomarkers to optimize the strategies for early detection of ovarian cancer. More funding from NFCR will surely help Dr. Bast raise his promising research on early detection to the next level, making it possible, down the road, for more women to win their race against this deadly disease.

NEXT STEPS: HOW YOU CAN HELP

These NFCR-supported research projects hold great promise for yielding more effective therapies for ovarian cancer. With more money, however, they could ramp up their efforts and accelerate progress. That is what the urgent plight of ovarian cancer patients demands, and that is what we at NFCR are committed to making possible.  Please click here if you would like to make a donation.