GSE181651 Senescence induction dictates response and resistance to chemo- and immunotherapy in preclinical models of ovarian cancer

Contributors : Stella V Paffenholz ; Camilla Salvagno ; Yu-jui Ho ; Matthew Limjoco ; Timour Baslan ; Sha Tian ; Amanda Kulick ; Elisa de Stanchina ; John E Wilkson ; Francisco M Barriga ; Dmitriy Zamarin ; Juan R Cubillos-Ruiz ; Josef Leibold ; Scott W LoweSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusHigh-grade serous ovarian carcinoma (HGSOC) is associated with a dismal prognosis. While most patients initially respond to platinum-based chemotherapy, they almost always acquire resistance, and only a small subset of HGSOC patients benefit from immune checkpoint blockade (ICB). To elucidate the disease mechanisms and factors underlying sensitivity and resistance to conventional and immune-based therapies, we developed a fast and flexible pre-clinical mouse model based on somatic introduction of HGSOC-associated genetic alterations into the ovary of immune competent mice using tissue electroporation. Tumors in these mice recapitulate both the proclivity of HGSOC to metastasize to the peritoneum and omentum and display histological, molecular, and treatment response features reminiscent of the human disease. Using this model, we show that the clinically observed increase in sensitivity of homologous recombination (HR) deficient ovarian tumors to platinum-based chemotherapy is driven by the preferential induction of senescence in the tumor cells. Intriguingly, HR-deficient (but not HR-proficient) tumors are uniquely sensitive to ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research