Repetitive Elements as a Therapeutic Opportunity to Intercept Ovarian High-Grade Serous Carcinoma

Project summary

This project will address the unmet clinical need to identify strategies to intercept early-stage ovarian high-grade serous carcinoma (HGSC) and improve HGSC response to immunotherapies in order to improve patient outcomes. Our approach to develop cancer interception strategies is to understand mechanisms of HGSC immune evasion during cancer initiation in order to identify vulnerabilities that can be exploited therapeutically.

Our preliminary data suggests that repetitive DNA sequences, derived in part from ancient viral infections, become active in precancerous lesions of the fallopian tube and induce an antiviral response that we describe as ‘viral mimicry’. We hypothesize that active viral mimicry underlies chronic inflammation that selects for cells best suited to evade the immune system before the HGSC tumor begins to form.

This project will determine: 1) how repetitive DNA drives chronic inflammation to select for immune evasion and 2) whether we can exploit this process therapeutically to intercept early HGSC and improve HGSC response to immunotherapies. This is important because multiple groups are developing approaches to improve early detection of HGSC. We expect this project to produce new therapeutic options to convert early diagnoses into actionable information that will shift HGSC management towards early-stage interception that will improve cure rates.

This grant was made possible in part by generous donations from the Mike & Patti Hennessy Foundation; Hope for Heather in memory of Heather Weeks; and Jennifer Willett in memory of Lynne Willett.