Histone deacetylases: Function in tumor development and therapeutic prospects (Review)

Histone deacetylases (HDACs), as key epigenetic regulators, serve a central role in tumorigenesis and progression by modulating chromatin architecture and gene transcription. In recent years, notable advances have been made in elucidating the pan-cancer mechanisms of HDACs and their inhibitors (HDACis), as well as in performing clinical studies, with their antitumor activity becoming a major research focus. The present review summarized the classification and molecular mechanisms of HDACs alongside their roles in various malignancies including ovarian cancer, endometrial carcinoma, glioma, osteosarcoma and multiple myeloma. The present review specifically elaborated on the relationship between particular isoforms, such as HDAC3, HDAC5, HDAC7 and HDAC11, and tumor progression, detailing associated signaling pathways. The present review systematically evaluated the current clinical applications of HDACis, examining both monotherapy and combination therapy efficacy alongside existing challenges. Furthermore, the present review discussed recent progress in structural modifications aimed at enhancing selectivity while reducing toxicity, as well as novel targeting strategies. Concluding with perspectives on HDAC-based therapies, the present review underscores the key importance of precision targeting and combinatorial approaches to improve patient outcomes in the future.