Fewer than half of women diagnosed with ovarian cancer live for five years or more. Sarah Adams, MD, hopes her new clinical trial will change this outcome. Adams recently opened a clinical trial at The University of New Mexico Comprehensive Cancer Center to test a new approach to defeat ovarian cancer. The clinical trial treats women whose ovarian cancer results from mutated BRCA genes. It uses one drug that kills the ovarian cancer cells and another that boosts the immune system in response to the dying cancer cells.
Ovarian cancer has unclear symptoms and no screening tests that catch it in its early stages. Often, ovarian cancer spreads to other organs before a woman even knows she has it. Surgery and chemotherapy can help women at the beginning of their treatment, and this gave Adams the idea for her new approach.
As a gynecologic oncologist, Adams performs surgery and prescribes chemotherapy for women with cancers of the female reproductive organs. Adams also conducts research. Her research suggested that women with BRCA-related ovarian cancer responded better to some chemotherapy drugs. Others’ research showed that other chemotherapy drugs not only kill cancer cells but also make the immune system more sensitive to them. Adams’ new treatment combines these approaches into what she thinks may be a powerful way to win against ovarian cancer.
BRCA is a set of genes we all carry. Each gene contains the instructions to produce a protein. BRCA proteins help DNA to repair itself when both of its strands break and completely split the molecule in two. If the BRCA genes are mutated, or changed, the resulting proteins do not work properly and the cell cannot repair its DNA. It dies unless it can resort to other repair methods.
Cells with mutated BRCA genes resort to using a DNA-repair protein called PARP. Adams’ therapy uses a type of drug called a PARP inhibitor, which keeps the PARP protein from its repair work. “If you knock out BRCA,” says Adams, “the cell can still live. If you knock out PARP, the cell can still live. But if you knock out both, the cell dies.”
The PARP inhibitor does not affect non-cancerous cells because they have working BRCA proteins to repair DNA. “It’s specific to cancer cells so it’s nicely targeted and there’s minimal toxicity,” says Adams. The therapy is also easy to dispense. “It’s a pill that people take orally,” she says.
Adams’ therapy combines the PARP inhibitor with a specific antibody. An antibody is a protein that attaches to a target cell. The antibody in Adams’ therapy helps one type of immune cell, called a T-cell, to find and devour ovarian tumor cells. Untreated ovarian tumors often produce chemical signals that keep T-cells away. But, the PAPR inhibitor combined with the antibody alert the entire immune system to the ovarian cancer cells.
Once the immune system can find the ovarian cancer cells, it can rid the body of them if the PARP inhibitor doesn’t kill them first. And because the immune system can remember how to respond to ovarian cancer cells, it can continue to rid the body of them if the cancer tries to come back. Adams hopes that this effect will give women long-lasting protection.
The clinical trial is currently open to women with BRCA1 or BRCA2 mutations. Either parent can pass these BRCA mutations to their children. People with BRCA mutations have a higher risk of getting breast and ovarian cancers and may have relatives who had these cancers at young ages.
In pre-clinical studies, this combination therapy got rid of tumors and helped mice to live longer. The clinical trial now makes the therapy available to women with BRCA gene mutations whose ovarian cancer has returned. “I’m very excited about the results we’ve seen so far,” says Adams, “and hopeful that this regimen can achieve long-term benefit for women with ovarian cancer.” Adams’s ultimate goal is to expand the therapy to help all women with ovarian cancer.
Watch videos and listen to interviews about the trial.
Sarah Adams, MD, is an Associate Professor in the Division of Gynecologic Oncology at the UNM Comprehensive Cancer Center. She is the Victor and Ruby Hansen Surface Endowed Professor in Ovarian Cancer Research. Trained at Harvard, the University of Chicago, and the University of Pennsylvania, Dr. Adams has a strong interest in translational research. Her work is focused on tumor immunology and the identification of new treatment targets for ovarian cancer. Dr. Adams was named a Liz Tilberis Scholar by the Ovarian Cancer Research Fund, and her research is also supported by the American Cancer Society. Dr. Adams has also been recognized for her teaching, and was awarded the Briscoe Award for Excellence in Teaching in 2012 and a National Faculty Teaching Award in 2010.
“A Phase 1-2 Study of the Combination of Olaparib and Tremelimumab in BRCA1 and BRCA2 Mutation Carriers with Recurrent Ovarian Cancer” is currently open for enrollment at the University of New Mexico Comprehensive Cancer Center. It is sponsored by the New Mexico Cancer Care Alliance and AstraZeneca. Eligible patients will be treated with the PARP-inhibitor as a pill they take at home every day and with monthly infusions of the immune checkpoint antibody. For more information, visit cancer.unm.edu/Combo-therapy-ovarian-CT or call 505-272-4946 and ask to speak to Sheri Westgate, RN, from the Gynecologic Oncology team.
Sarah Adams, MD, wishes to thank the Ovarian Cancer Research Fund and the Oxnard Foundation for their support of this work.
The University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 500-mile radius. Its 125 board-certified oncology specialty physicians include cancer surgeons in every specialty (abdominal, thoracic, bone and soft tissue, neurosurgery, genitourinary, gynecology, and head and neck cancers), adult and pediatric hematologists/medical oncologists, gynecologic oncologists, and radiation oncologists. They, along with more than 500 other cancer healthcare professionals (nurses, pharmacists, nutritionists, navigators, psychologists and social workers), provided cancer care for nearly 60 percent of the adults and children in New Mexico affected by cancer. They treated 11,249 patients in 84,875 ambulatory clinic visits in addition to in-patient hospitalizations at UNM Hospital. These patients came from every county in the State. More than 12 percent of these patients participated in cancer clinical trials testing new cancer treatments and 35 percent of patients participated in other clinical research studies, including tests of novel cancer prevention strategies and cancer genome sequencing. The 130 cancer research scientists affiliated with the UNMCCC were awarded almost $60 million in federal and private grants and contracts for cancer research projects and published 301 high quality publications. Promoting economic development, they filed more than 30 new patents in FY16, and since 2010, have launched 11 new biotechnology start-up companies. Scientists associated with the UNMCCC Cancer Control & Disparities have conducted more than 60 statewide community-based cancer education, prevention, screening, and behavioral intervention studies involving more than 10,000 New Mexicans. Finally, the physicians, scientists and staff have provided education and training experiences to more than 230 high school, undergraduate, graduate, and postdoctoral fellowship students in cancer research and cancer health care delivery. Learn more at www.cancer.unm.edu.
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