Introduction: High grade serous ovarian cancer (HGSOC) patients initially respond well to therapy, but subsequent treatment resistance and relapse demands further research to improve survival. HGSOC treatment induces DNA damage, which can lead to therapy-induced senescence (TIS), a stable proliferative arrest with opposing roles in cancer. A short-term positive relation between TIS and survival prompted the “One-Two Punch” clinical trial, where senescence is induced by treatment, then removed with senolytic drugs to avoid late adverse effects. We believe understanding TIS is crucial to developing novel approaches to improve patient prognosis. We aim to identify a treatment-response signature over time in patient-resembling models, uncovering early resistance factors and providing actionable targets to prevent relapse.

Methods: We developed patient-derived xenografts (PDX) mice from HGSOC patient tumors. PDX tumors harvested 7 days post-treatment and matched patient samples underwent bulk RNA sequencing, RT-qPCR, single-cell multiplex immunofluorescence and ELISA. Findings were compared with public single-cell datasets of patients pre/post-treatment.  

Results: We successfully derived 4 PDX from 4 HGSOC patients. Analyses revealed PDX closely mimic their matched patient, while also reproducing inter-patient heterogeneity. Early treatment-response pathways involved TIS or inflammation, confirming our hypothesis. A similar TIS/inflammation signature was found in post-treatment patient cancer cells from public datasets.

Conclusions: Our findings highlight pivotal roles for TIS and inflammation in HGSOC’s early treatment response. Ongoing efforts involve single-cell sequencing of (~200) HGSOC patients and diverse models at various post-treatment timepoints. Resulting transcriptomic Atlas aims to offer the first exploration of HGSOC’s treatment-response signature over time, to expedite identification of targets with direct clinical relevance for improved patient survival.