Abstract 2449 Epigenetic Regulation of Therapy-Induced Senescence and Senescence Escape in Hepatoma Cells

Hepatocellular carcinoma (HCC) stands as a prevalent and lethal form of liver cancer globally, necessitating effective therapeutic strategies. Therapy-induced senescence (TIS) has emerged as a promising approach in HCC treatment, yet the potential escape of tumor cells from TIS poses a challenge, contributing to cancer recurrence. Recognizing the pivotal role of epigenetic alterations in cellular senescence and cancer, with their reversible nature offering promise for anti-cancer therapies, we aim to unravel the epigenetic regulation of TIS and the phenomenon of senescence escape in hepatoma cells. In this study, we employed various drug conditions to establish in-vitro HCC models, confirming TIS and senescence escape through morphological and target marker alterations. Our next steps involve utilizing H3K27ac HiChIP to comprehensively profile three-dimensional (3D) enhancer landscape changes in proliferating, TIS, and senescence escaped cells. This approach aims to pinpoint crucial alterations and identify key regulators, including transcriptional factors that orchestrate the transition. In addition, RNA-seq will be employed to elucidate the correlation between changes in genome architecture and gene expression programs. This work will shed light on the mechanism of chromatin dynamics in regulating TIS and its escape and offer new avenues for therapeutic interventions of HCC. We express our sincere gratitude to the National Institute on Aging (NIA) and Cancer Prevention and Research Institute of Texas (CPRIT) for their funding support, which has been instrumental in advancing our research endeavors.