Accelerating progress in ovarian cancer
Sometimes called the “silent killer,” ovarian cancer is frequently diagnosed without obvious symptoms when it has already advanced to a late stage and is difficult to treat. In fact, more than 14,000 women die from ovarian cancer in the U.S. annually. Researchers and physicians at the University of Chicago Medicine Comprehensive Cancer Center are approaching deadly ovarian cancer from all perspectives – from cancer prevention to understanding cancer mechanisms, developing novel therapies and improving survivorship.
For women who may be at a higher risk of ovarian cancer because of genetic factors, personalized risk assessment and prevention recommendations are critical for health care decision-making. Gynecologic oncologist Iris Romero, MD, leads UChicago Medicine's Hereditary Breast and Ovarian Cancer Risk and Prevention Clinic with Olufunmilayo Olopade, MD, to provide screening and coordinated care for these women and their families.
Current screening options do not always detect ovarian cancer at a treatable stage even in these high-risk women. “This group of patients can’t rely on screening as a way to manage their cancer risk,” Romero said. Many of these women choose surgery in which the ovaries are removed despite other health consequences.
Romero serves as the Comprehensive Cancer Center’s lead investigator for the national WISP trial (for Women Choosing Surgical Prevention) to test whether delaying removal of the ovaries can prevent or delay sexual dysfunction in women who are high risk for developing ovarian cancer. The project is also addressing how to increase access to genetic testing to identify individuals as high-risk due to hereditary factors.
Developing novel therapeutic approaches to ovarian cancer requires a deeper understanding of the molecular causes and evolution of the disease. A team led by Ernst Lengyel, MD, PhD, chair of obstetrics and gynecology, discovered last year that while some ovarian cancers originate in the fallopian tubes, some originate outside the fallopian tubes and metastasize there, challenging current paradigms about prevention and treatment.
For women who may be at a higher risk of ovarian cancer because of genetic factors, personalized risk assessment and prevention recommendations are critical for health care decision-making.
Lengyel’s pioneering work has also painted a more complete picture of how the ovarian cancer microenvironment — the surrounding cells and tissues — promotes cancer spread. His laboratory has created a novel three-dimensional co-culture system to mimic the interactions of tumor cells with the microenvironment. They recently found that microenvironment-associated fibroblasts mobilize glycogen as an energy source in ovarian cancer cells to promote metastasis (Curtis et al., Cell Metabolism 29:141-55, 2019). This finding has implications on being able to cripple tumor cells by cutting off this energy source.
Furthermore, Lengyel recently characterized some of the molecular signals from fat cells that promote the spread of ovarian cancer cells in the abdominal cavity (Ladanyi et al., Oncogene 37:2285-2301, 2018) and identified a new biomarker, called CT45, associated with treatment success and patient outcomes (Coscia et a., Cell 175:159-70, 2018). Extension of these promising laboratory results, and their translation into the clinic, will be the focus of future studies by Lengyel and his team.
Leadership in clinical trials is another key way that Comprehensive Cancer Center investigators are working to improve treatment and outcomes for patients with ovarian cancer, especially those with advanced cancer. Oncologists Gini Fleming, MD, and John Moroney, MD, are national leaders in conducting clinical trials, from early-phase trials testing drug safety to large phase III trials assessing the potential benefit of new treatments compared to the standard of care.
Recently, Fleming and colleagues tested a new type of drug called a hypomethylating agent in combination with chemotherapy in patients with advanced ovarian cancer who were previously treated with other agents, and were resistant to the chemotherapy. This multicenter phase I study showed that this combination therapy was safe and had anti-cancer activity, supporting a follow-up randomized phase II trial (Matei et al., Clin Cancer Res 24:2285-93, 2018).
Fleming is also an integral member of the Stand Up to Cancer-Ovarian Cancer Research Fund-National Ovarian Cancer Coalition (NOCC) Ovarian Cancer Dream Team testing the effects of a new class of anticancer drugs called PARP inhibitors in ovarian cancers with specific molecular defects in how cells repair damage to their DNA. Because these new therapies are already used for some inherited forms of breast cancer, their application to ovarian cancer treatment could be rapid.
Making improvements in the quality of life, not just quantity of life, for ovarian cancer patients is motivating for the Comprehensive Cancer Center ovarian cancer team. The NOCC partnered with the Comprehensive Cancer Center for their annual education event in September, and the ovarian cancer team participates annually in — and has raised tens of thousands of dollars for — the NOCC’s Illinois Chapter Run/Walk to Break the Silence on Ovarian Cancer.
Our physicians and scientists recognize that the biggest impact comes from working side by side with patients, caregivers, advocacy organizations, community partners and the public to promote discovery, awareness and survivorship.