Molecular Cross Talk Between Estrogens and Progestogens in Endometrial Cancer
Abstract
This project is focused on the topic of endometrial cancer and the military health focus area of mission readiness, while addressing the overarching challenge to identify strategies to predict treatment resistance, recurrence, and the development of advanced disease. Endometrial cancer care needs to be improved. Endometrial cancer, which arises in the lining of the uterus, is the most common gynecological cancer with increasing rates and deaths throughout the world. Unfortunately, outcomes for women following an endometrial cancer diagnosis haven’t gotten better during the last 50 years and improvements in the care of women with endometrial cancer are desperately needed. We believe that improvement in the clinical care of women with endometrial cancer will come from both the development of new treatment strategies and better decision making when using current therapies. The goal of this proposal is to better understand the molecular effects of progestins (synthetic progesterone) and use these findings to discover biomarkers of progestin treatment success in endometrial cancer patients. Biomarkers of progestin treatment success will help women make a difficult decision. Progestins are the only approved drug for the treatment of primary endometrial cancer, having been approved in 1972. Despite the use of progestins for several decades and the fact that no other drug treatments are approved, physicians have no test or biomarker to determine the likelihood that a woman will respond well to treatment. Since progestins are only effective in approximately half of patients and are the only option for women that want to maintain their fertility, women are faced with a difficult decision that is similar to a coin toss: Should they take a riskier treatment and preserve the opportunity to become pregnant or should they undergo surgery, an effective treatment, and lose their fertility? A biomarker that predicts progestin treatment success would empower women to make an informed decision about a difficult choice. A major goal of this project is to find genes whose expression levels will indicate if progestin therapy is likely to work. The successful completion of this project will lead to key validation studies and hopefully the launch of a clinical test in a 5-10 year window. Studies into progesterone and estrogens could uncover new drug development targets In addition to the near-term goals of developing progestin biomarkers, we also aim to discover key proteins that help shift the balance from progesterone, which stops tissue growth, to estrogens, which promote tissue growth. These key proteins would serve as candidates for new endometrial cancer treatments. In addition to treatment for endometrial cancer patients, we may also uncover new approaches for preventing endometrial cancer development. Since hormone imbalance is central to endometrial cancer risk, our findings may point to new ways to mitigate this risk in high-risk patients, including patients diagnosed with endometrial hyperplasia. While we are unsure of which proteins we’ll find, the discovery of these drug targets could lead to further studies and eventually clinical trials of treatments/preventatives that either work with progestins or in place of progestins. Any new treatment options that we discover would represent a large step forward in the care of women with endometrial cancer. Relevance to Military Health: The proposed project addresses the military health focus area of gaps in cancer research that may affect mission readiness. A better understanding of progestin therapy response could aid in women undergoing more effective and less intense treatment of endometrial cancer. These improvements would minimize Service Members, Veterans, and their family members’ time in the hospital and risk of serious health problems.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310945
Entities
People
- Jay Gertz
Organizations
- United States Army
- University of Utah