While 80-85% of high grade serous ovarian cancers (HGSOC) undergo dramatic regression with platinum/taxol-based chemotherapies, the vast majority of tumors relapse, initially displaying sensitivity to a repeat course of platinum/taxol, and then undergoing relapses of progressively more resistant tumor populations. The chemo-sensitivity of relapsed tumors indicates that primary residual tumor cells that survive chemotherapy represent drug tolerant “persister” cells, rather than genetically resistant cells, and suggests that therapies which kill these cells or prevent their development could significantly delay or prevent recurrence. Thus, it is of critical importance to characterize such drug-tolerant cells, understand their heterogeneity, identify cellular programs that are required for resistance, develop strategies to target these therapeutic vulnerabilities and predict outcome of chemotherapy. In my presentation, I will discuss what we have learned about these critical issues from scRNAseq and multiplex imaging of patient HGSOC tumors before and after chemotherapy treatment.
This work is being done in collaboration with the labs of Boris Winterhoff, Andrew Nelson, Ronny Drapkin, Gottfried Konecny, and Dennis Slamon.