Introduction: Cell senescence is a key tumor suppression mechanism that forces precancerous cells to stop dividing. In addition to oncogenes, senescence can be induced by stresses including DNA damage and many cancer therapies. Interestingly, while therapy-induced senescence (TIS) can be beneficial as it also halts tumor growth, there are cases where senescent cells escape cell cycle arrest and resume proliferation, leading to treatment resistance. Epithelial ovarian cancer (EOC), characterized by a high mortality rate and frequent relapses, provides a pertinent context for investigating TIS. We propose that the accumulation of senescent cells in EOC tumors can be detrimental to the patient, potentially leading to relapse and contributing to the poor outcomes associated with this disease. Understanding the mechanisms of TIS is therefore crucial for improving the efficacy of current treatments and developing new therapeutic strategies to target EOC.

Methods: We utilized the EOC cell line TOV21G and induced senescence through a treatment regimen combining the first line chemotherapy agents carboplatin and paclitaxel. Following this treatment, we allowed 7 days for senescence to establish in these cells before conducting our analysis.

Results: We observed a significant decrease in the expression of MYC transcriptional targets. Consistent with these findings, we observed a decrease in MYC protein levels, while the transcript was slightly increased in the senescent cells. To understand the regulation mechanisms of MYC levels, we employed gain and loss of function models. Our results suggest that decreased MYC activity is necessary for EOC in TIS.

Conclusion: Our findings highlight the importance of MYC regulation during TIS and suggest that MYC levels could predict the fate of cancer cells after chemotherapy treatment. This discovery is particularly significant given that MYC is a potential pharmacological target that is amplified in many cancers including EOC.