Treating Advanced Uterine Endometrial Cancer by Reactivating p53
Abstract
Over the past decades, only a few types of cancers have increased in incidence, morbidity, and mortality. Cancer of the uterus (endometrial cancer) is one of these dangerous malignancies. Sadly, clinical outcomes for women with endometrial cancer are worse today than in 1980s. The poor outcomes are driven by the significant increase in high-risk, aggressive forms of endometrial tumors called serous and high-grade endometrioid cancer. Therapy for endometrial cancer has not improved since the 1990s – currently, every woman with a high-risk form of endometrial cancer receives exactly the same baseline treatment: surgery followed by chemotherapy with a taxane and a platinum compound. We lack an understanding of how each tumor may be different, requiring alternative management. Fortunately, we are now entering the age of personalized medicine, and we finally understand the gene mutations that provide an opportunity for personalized treatments. This project will test a class of drugs called p53 reactivators, specifically designed to overcome mutations in genes that encode mutant proteins (p53 and BRCA) that drive tumor progression. Such mutations occur in the most dangerous forms of endometrial cancer. Surprisingly, p53 reactivators, although approved for other forms of cancer, have not yet been tested clinically in endometrial cancer patients. Our proposal will take advantage of banked endometrial cancer cells previously harvested with permission directly from consenting patients’ tumors. These unique cell models, called organoids, recapitulate patient responses to drugs when grown in the laboratory and are highly relevant scientifically. The results of our studies will provide the necessary proof of principle to support the new clinical trials that are urgently needed to improve the care of women with endometrial cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210754
Entities
People
- Kimberly K Leslie
Organizations
- Health Sciences Center, University of New Mexico
- United States Army