Senescence induction dictates response to chemo- and immunotherapy in preclinical models of ovarian cancer.

ABSTRACT: High-grade serous ovarian carcinoma (HGSOC) is a cancer with dismal prognosis due to the limited effectiveness of existing chemo- and immunotherapies. To elucidate mechanisms mediating sensitivity or resistance to these therapies, we developed a fast and flexible autochthonous mouse model based on somatic introduction of HGSOC-associated genetic alterations into the ovary of immunocompetent mice using tissue electroporation. Tumors arising in these mice recapitulate the metastatic patterns and histological, molecular, and treatment response features of the human disease. By leveraging these models, we show that the ability to undergo senescence underlies the clinically observed increase in sensitivity of homologous recombination (HR)-deficient HGSOC tumors to platinum-based chemotherapy. F

SUBMITTER: Paffenholz SV 

PROVIDER: S-EPMC8812522 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature