Recent Progress in HDAC-Based Dual-Target Inhibitors for Colorectal Cancer

Colorectal cancer (CRC) remains one of the leading causes of cancer-related incidence and mortality worldwide, with accumulating evidence indicating that its tumorigenesis and progression are tightly linked to epigenetic dysregulation. Histone deacetylases (HDACs) are key epigenetic regulators involved in gene transcription, cell-cycle regulation, and cancer progression, whereas the therapeutic benefits of conventional HDAC inhibitors are frequently compromised by limited selectivity and resistance development. Recently, dual-target HDAC inhibitors (HDACis) have attracted considerable attention as an emerging paradigm in anticancer drug development. These multitarget strategies can simultaneously enhance synergistic antitumor efficacy and alleviate the compensatory resistance commonly associated with single-target therapies via multi-mechanistic interventions. Accordingly, the concurrent modulation of HDACs and additional therapeutic targets represents a viable therapeutic strategy for CRC. In this review, we systematically summarize the recent progress of dual-target HDAC is in CRC treatment, with particular emphasis on their therapeutic potential and implications for future translational research and clinical practice.