Unfolding the role of HDAC2 in the epigenetic puzzle of cancer: A dive into molecular pathways for precision-driven multi-target therapy.

Given the pivotal role of histone deacetylase 2 (HDAC2) in cancer development and the inherent complexity of tumor progression, including resistance to single-target therapies, dual or multi-target inhibitors present a promising strategy for offering enhanced therapeutic efficacy. In this context, targeting HDAC2 and its critical signaling pathways represents an innovative direction in precision-driven cancer treatment, emphasizing their potential in addressing cancer heterogeneity and optimizing therapeutic efficacy. Despite the growing body of evidences in this context, reviews on molecular intricacy behind the HDAC2-mediated epigenetic regulation of cancer are not well looked into. Therefore, the present review aims to elaborately underscore the role of HDAC2 and the underlying HDAC2-driven signaling mechanisms reported in recent preclinical and clinical studies related to tumor initiation, development, and progression across various cancers. The review also explores the multi-target HDAC2 inhibitors as well as those in clinical trials that act in conjunction with other cancer-related signaling proteins, highlighting their potential as promising targets for enhanced treatment outcomes. All in all, this study advances a strategically overlooked yet critically potent mechanistic framework that holds transformative potential to intercept cancer at its molecular epicenter.