$15 million Program Project Grant from the NCI for research in endometrial cancer – Dana-Farber Cancer Institute
Dana-Farber Cancer Institute shared a post on LinkedIn:
“Dana-Farber physician-scientists have received a five-year, $15 million Program Project Grant from the National Cancer Institute (NCI) for research in endometrial cancer, a malignancy of the inner lining of the uterus that affects more than 68,000 women per year in the United States. It is one of only two forms of cancer in which survival rates have not significantly improved since the mid-’70s.
The grant will fund three projects that focus on replication stress, a key characteristic of many endometrial cancers, especially high-grade and aggressive forms. Replication stress slows or stops DNA duplication during the cell cycle, potentially setting the stage for mutations or other genomic abnormalities. Each project explores a different approach to targeting replication stress as a vulnerability in endometrial cancer cells.
“The incidence of endometrial cancer in the U.S. is rising at an overall rate of 1% per year and is increasing even faster among non-white populations, explains Ursula Matulonis, MD, chief of Gynecologic Oncology and co-principal investigator of the program, with Gynecologic Oncology colleagues Panagiotis A. Konstantinopoulos, MD, PhD, and Joyce Liu, MD, MPH, director of translational research and associate chief and director of clinical research in the department, respectively. “At the same time, there are racial and ethnic disparities in both incidence and survival for this disease, with Black women at a higher risk to develop the disease, and more likely to die from it, than white women. These trends make it urgent that we develop new treatment strategies, particularly for patients with advanced or relapsed cancer.
The three projects are:
• Study of the molecular mechanism by which targeted drugs called WEE1 inhibitors act in recurrent uterine serous cancer, an uncommon but aggressive subtype of endometrial cancer, and in uterine cancer harboring a mutation in the p53 gene. The project builds on a clinical trial led by Liu and Konstantinopoulos that found that adavosertib, a WEE1 inhibitor, has significant activity in these cancers.
• Research into the hypothesis that inhibiting the PI3K protein pathway with a drug agent can increase replication stress in endometrial tumor cells and work in combination with targeted drugs known as ATR inhibitors.
• Investigating the possibility of targeting two types of checkpoint proteins in endometrial cancer cells. One acts as a checkpoint on repair of DNA damage while the other acts as a checkpoint on the immune response to cancer.
Each of these projects has great potential for improving the treatment of endometrial cancer by targeting replication stress, remarks Matulonis.
Additional project leaders associated with the grant include Dana-Farber researchers Dipanjan Chowdhury, PhD, principal investigator of the Chowdhury Lab, and Jean Zhao, PhD, principal investigator of the Zhao Lab.