Abstract Ovarian cancer is a disease that affects approximately 1 in 91 women. The most lethal and common form of ovarian cancer is high-grade serous ovarian cancer (HGSOC). Current precision-based medicine approaches to treating HGSOC are limited to PARP inhibitors for BRCA mutant and homologous combination deficient patients. There is a desperate need for more options for ovarian cancer patients. Preferably these new treatments would both work for a large population of those with high-grade serous ovarian cancer and be precise to a specific biomarker of the disease. We have shown that one possible biomarker for disease treatment is the MYC and HSF1 (Heat Shock Factor 1) co-amplification which occurs in approximately 31% of ovarian cancer patients. We have shown in cell viability assays, colony formation, and spheroid assays that ovarian cancers with this co-amplification are more sensitive to the PLK1i volasertib compared to ovarian cancers that do not carry this co-amplification. Since volasertib is not being pursued clinically as a monotherapy due to its own adverse effect concerns, we aimed to find if there are other drugs that HGSOC with the MYC and HSF1 co-amplification are sensitive to. Considering that HSF1 and MYC are both transcription factors, we hypothesized that an epigenetic inhibitor could be an effective disruptor of MYC and HSF1 activity in HGSOC. We found in a drug screen of 479 drugs that ovarian cancers with this co-amplification are sensitive to class I HDAC inhibitors. We have shown using one of these top-performing HDAC class I inhibitors, entinostat, that MYC and HSF1 protein levels are decreased after 24 hours of treatment. Further studies will aim to establish the mechanism between how HDAC class I inhibition leads to a decrease in MYC and HSF1 protein and if this mechanism is responsible for cell death seen after 48 hours of treatment in unique to MYC and HSF1 co-amplified ovarian cancer. Citation Format: Matthew S. O'Malley, Imade Williams, Haddie DeHart, Bobby Walker, Vrushabh Ulhaskumar, Pranav Jothirajah, Haimanti Ray, Lisa M. Landrum, Joe R. Delaney, Kenneth P. Nephew, Richard L. Carpenter. MYC-HSF1 coamplification as a biomarker for treatment sensitivity in high-grade serous ovarian cancer abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85 (18Suppl): Abstract nr A040.
O’Malley et al. (Fri,) studied this question.