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The alkylating agent platinum is first-line chemotherapy treatment for high-grade serous carcinomas (HGSC) of tubal-ovarian origin. Platinum compounds cause DNA damage and induce apoptotic cell death in the bulk tumor population. However, subpopulations of tumor cells may exhibit diverging behaviors from the bulk tumor due to an alternate stress response that diverts tumor cells from apoptotic death. In this study, we identified a salvage survival pathway in which G2-arrested tumor cells bypassed apoptosis and progressed through aberrant mitotic events to then emerge as a distinct subpopulation of viable large hyperploid cells but with uncertain long-term propagation potential. Platinum-induced large hyperploid cells were flow sorted and showed rare regrowth capacity as compared to their more proficiently regenerating non-hyperploid counterparts. However, detailed time-lapse microscopy provided direct evidence that these hyperploid cells were mitotically active and could divide successfully to produce viable daughter cells. The hyperploid survival response was observed across different cell lines and utilization of this survival pathway was dependent on the strength of the G2-M checkpoint. Conceivably, this salvage survival strategy may contribute to increased genomic diversity of the regenerating tumor cell line through a coupled hyperploidization and de-polyploidization process that may be relevant for drug resistance.

Implication Statement Medical schools have a responsibility to ensure students meet and advocate for the needs of the community. However, addressing the social determinants of health is not always emphasized in clinical learning objectives. Learning logs are useful tools that can engage students to reflect on clinical encounters and direct students in their learning to target the development of highlighted skills. Despite their efficacy, the use of learning logs in medical education is largely applied towards biomedical knowledge and procedural skills. Thus, students may lack competence to address the psychosocial challenges involved in comprehensive medical care. Social accountability experiential logs were developed for third year medical students at the University of Ottawa to address and intervene on the social determinants of health. Students completed quality improvement surveys and results demonstrated this initiative to be beneficial to their learning and contributed to greater clinical confidence. Experiential logs in clinical training can be adapted across other medical schools and tailored to fit the needs and priorities of each institution’s local communities.

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