VINCENT DEPARTMENT OF OBSTETRICS AND GYNECOLOGY


Conquering Women’s Cancers

Medical breakthroughs often arise from collaborations between scientists in different departments and institutions. Below are examples of how the Vincent Center for Reproductive Biology (VCRB) is working with other scientists to find new ways to diagnose and treat women’s cancers. The VCRB is a funding priority of The Vincent Memorial Hospital Foundation (VMHF), which last year infused $685,000 into this nationally acclaimed OB/GYN laboratory, where researchers seek to identify innovative pathways to advance women’s health. 

Gynecologic Oncology Leadership Group

Gynecologic Oncology Leadership Group

A new Gynecologic Oncology Leadership Group at Massachusetts General Hospital is coordinating an all-out effort to conquer cancers of the female reproductive system — from early detection to personalized treatment options. “The biggest fundamental change in our gynecologic cancer research initiative has been creating an organized leadership group representing surgery, medicine and basic research,” said Eric Eisenhauer, MD (at left in photo), chief of the Division of Gynecologic Cancer in the Vincent Department of OB/GYN. Meeting weekly, the group also includes scientist Bo Rueda, PhD (center), director of the Vincent Center for Reproductive Biology, who conducts basic research in gynecologic cancer and also oversees an extensive tumor bank, a treasure trove for lab investigators. The third specialist is medical oncologist David Spriggs, MD (right), director of the Gynecologic Cancer Program at the Mass General Cancer Center, who offers systemic treatment options such as chemotherapy and immunotherapy for women’s cancers. In addition, a forum of approximately 15 physicians and scientists from Mass General and MIT meets monthly. Together, they are speeding the translation of lab findings about molecules, genes and cells into possible drug interventions, which are tested in cell lines, then animals and possibly human patients. A key goal is to develop immunotherapies for ovarian cancer, diagnosed in 20,000 U.S. women each year and causing more deaths than any other gynecologic cancer. One aim of immunotherapy is to block cancer cells’ ability to avoid the immune system, allowing the immune system to recognize and destroy cancer cells as foreign invaders. At the heart of this approach is personalized medicine. All ovarian cancer patients at Mass General undergo genetic testing for nine hereditary mutations, then treatment is tailored to their genetic profile and multi-modality protocols emerging from clinical studies nationwide. “Thirty years ago, the life expectancy of a woman with ovarian cancer was less than 2 years,” said Dr. Eisenhauer. “Today, effective surgery and novel medical therapies allow patients to live on average 6 to 10 years, and emerging treatments promise to push that out even further. Many of these positive results are possible because of The Vincent Memorial Hospital Foundation, which for more than 25 years has provided funding for the VCRB and resources for Vincent fellows and trainees. The Vincent’s support is making a huge difference.”

New Drug Therapy for Recurrent Ovarian Cancer

New Drug Therapy for Recurrent Ovarian Cancer

In a classic example of “bench to bedside” medical progress, lab research conducted by Bo Rueda, PhD, director of the Vincent Center for Reproductive Biology (VCRB), has culminated in a clinical trial for a new drug therapy designed to combat recurrent ovarian cancer. The trial, launched in January 2021 by a biotech company, was based, in part, on preclinical work completed here at Massachusetts General Hospital. The Phase 1 study will accrue 205 patients to determine safe doses of a new drug called SGN-STNV. This highly specific antibody-drug conjugate is designed to target a tumor-associated antigen called STN, which Dr. Rueda has shown is elevated in chemotherapy-resistant ovarian cancer and associated with decreased survival. The trials prospectively will then advance to the next phase to determine the drug’s effectiveness against recurrent ovarian cancer and other advanced solid tumors. Because this same antigen also is present in in chemo-resistant pancreatic, colon and gastric malignancies, research performed in the VCRB may have lifesaving potential beyond gynecologic cancers.

Detecting DNA of High-grade Serous Ovarian Cancer in the Bloodstream

Detecting DNA of High-grade Serous Ovarian Cancer in the Bloodstream

Sara Bouberhan, MD, a Mass General medical oncologist and an instructor in medicine at Harvard Medical School, is striving to detect circulating tumor DNA in the bloodstream of patients with high-grade serous ovarian cancer — the most fatal gynecologic cancer in the United States. To help oncologists make clinical decisions with more precision, she is working to develop a liquid biopsy — a blood test that detects damaged DNA from ovarian cancer cells. These pursuits also may lead to a much-needed screening tool for early detection and treatment of ovarian cancer. Another potential application of a liquid biopsy is identifying which patients have been cured with front-line therapy and those who are still receiving but not benefiting from chemotherapy, causing them to experience toxicity unnecessarily. She has been pursuing this area of research at Mass General since 2019, when she joined the Department of Medicine and also began collaborating with VCRB director Bo Rueda, benefiting from his mentorship. Dr. Bouberhan also draws upon the VCRB’s tissue bank, which over the past 14 years has collected thousands of gynecologic samples useful in identifying genes or proteins and their signaling pathways that contribute to malignant transformation of cells and treatment resistance. In 2020, she was the lead author of a review article in the journal Cancers that describes recent scientific advances that may improve ovarian cancer treatment. Even with surgery and chemotherapy, many patients live less than five years. But today, scientists know that ovarian cancer often harbors defects in DNA-repair mechanisms, and several new treatment approaches are focusing on exploiting this genetic instability.

Cancer Studies Lead to Fertility Discovery

Cancer Studies Lead to Fertility Discovery

Cheng Wang, PhD, an investigator in the Vincent Center for Reproductive Biology (VCRB), recently discovered that the protein YAP1 contributes to female fertility. His previous studies had shown YAP1 is highly expressed in granulosa cells in ovarian follicles and promotes the progression of ovarian cancer. His new findings show that follicle development and successful reproduction rely on balanced expression and activation of YAP1, making it a promising target for treatment of infertility associated with abnormal ovarian granulosa cell function. This research is a prime example of how one area of basic science (cancer) can illuminate another (fertility).