2024-25 Team Scient Grantees: Sara Buhrlage, PhD, Ronny Drapkin, MD, PhD, & Jarrod Marto, PhD
About Project
Harnessing Epigenetic Alterations in the Fallopian Tube to Develop Early Interception Strategies in Ovarian Cancer
PROJECT & PROGRESS SUMMARY
High-grade serous ovarian cancer (HGSOC) is a heterogeneous and lethal gynecologic malignancy. Most women are diagnosed at late stage where 5-year survival rates remain stubbornly poor. It has long been thought that early detection would reduce mortality associated with HGSOC. Strikingly, results from the recent United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) may shift the paradigm for how we view clinical intervention for this disease. In short, the UKCTOCS study found that detection of ovarian cancer at stage I or II does not reduce mortality. In light of this provocative finding, our interdisciplinary team from UPenn and Dana-Farber is focused on ‘early interception’. This emerging concept combines the notion of molecular disease markers with cutting edge small molecule pharmacologic strategies. In essence we are asking if molecular markers which may have been considered ‘undruggable’ with traditional approaches, can now be targeted with modern genetic and chemical biology tools to stop ovarian cancer in its tracks before it can get a foothold in the reproductive tract tissues of an otherwise healthy woman.
Our team has been at the forefront of characterizing fallopian tube epithelial cells (FTSEC) as the cell-of-origin for HGSOC. We recently found that a specific DNA modification was required to maintain FTSEC in a benign state. Loss of this specific DNA modification resulted in different gene expression and ultimately the malignant transformation of FTSEC. The focus of our work in this proposal is to develop and use state-of-the-art chemical biology approaches to harness this modification as an early interception target in HGSOC.
PRESS
October 23, 2017: OVARIAN CANCER MAY ACTUALLY ARISE IN FALLOPIAN TUBES
