Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer
Abstract
Efforts to understand and find new treatment options for high-grade serous ovarian cancer (HGSOC) have been confounded by a paucity of immune-competent models that accurately reflect the genetics and biology of the disease. Here, we leverage somatic tissue engineering to develop a fast and flexible immune-competent mouse model of HGSOC and reveal mechanistic insights into factors that dictate the response of ovarian tumors to conventional chemotherapy and immune checkpoint blockade. Our results identify a genotype-dependent therapy-induced senescence program that mediates sensitivity and resistance to first line chemotherapy and point to strategies to harness the senescence program to sensitize ovarian tumors to immune checkpoint blockade.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 26, 2022
- Source ID
- 10.1073/pnas.2117754119
Entities
People
- Amanda Kulick
- Camilla Salvagno
- Dmitriy Zamarin
- Elisa De Stanchina
- Francisco M. Barriga
- John E. Wilkinson
- Josef Leibold
- Juan R Cubillos-Ruiz
- Matthew Limjoco
- Scott W. Lowe
- Sha Tian
- Stella V. Paffenholz
- Timour Baslan
- Yu-jui Ho
Organizations
- Cornell University
- German Research Foundation
- Howard Hughes Medical Institute
- Memorial Sloan Kettering Cancer Center
- National Cancer Institute
- National Institutes of Health
- Stand Up to Cancer
- United States Department of Defense
- University of Michigan
- University of Tübingen
- Weill Cornell Medicine