Epigenetic Regulation of Cellular Senescence in Gastrointestinal Cancer

Abstract Gastrointestinal (GI) cancers, encompassing malignancies of the digestive tract, are significant contributors to global cancer morbidity and mortality. Despite advancements in molecular insights and therapeutic approaches, the prognosis remains dismal due to persistent treatment resistance and metastasis. Cellular senescence, a permanent halt in the cell cycle due to various stressors, playing dual roles in tumor suppression and promotion. Interestingly, epigenetic modifications-heritable shifts in gene level without altering the DNA sequence-are identified as key regulators of cellular senescence. These modifications, such as DNA methylation, histone alterations, chromatin remodeling, and non-coding RNA interactions, shape the senescence phenotype and influence cancer progression and therapy resistance. Recent research underscores the potential of "pro-senescence" therapies, leveraging epigenetic modulators and senescence-inducing agents to counteract GI cancer progression. This review explores the relationship between cellular senescence and epigenetic regulation in the context of GI cancer highlighting the characteristics of senescence, the epigenetic mechanisms at play, their impact on GI cancer senescence, and the promising horizon of anti-senescence therapies. Through a detailed examination of current research, we propose that understanding the intricacies of epigenetic regulation in cellular senescence offers a novel vista for therapeutic intervention in GI cancers, potentially paving the way for improved clinical outcomes.