Abstract
ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, has emerged as a pivotal tumor suppressor altered in a broad range of human malignancies. Its frequent inactivation across diverse cancer types has revealed pleiotropic roles that intersect multiple Hallmarks of Cancer. In this review, we integrate current knowledge on how ARID1A loss influences cellular processes including proliferative signaling, resistance to cell death, genomic instability, metabolic reprogramming, immune evasion, and more. We discuss the context-specific consequences of ARID1A deficiency, its cooperation with other oncogenic events, and its implications for therapeutic vulnerability-particularly in the realm of synthetic lethality and immune modulation. By mapping ARID1A's functional impact onto the established hallmarks framework, we highlight its centrality in cancer biology and underscore opportunities for biomarker-driven strategies and targeted interventions. Understanding ARID1A's multifaceted roles offers a compelling lens through which to explore chromatin dysregulation in cancer and guide translational advances.