HDAC Inhibitors in Hematological and Solid Tumor Therapy: CurrentSuccess, Challenges, and Future Directions

Abstract: The abnormal HDAC activity contributes to the induction of cancer by disturbing normal cellular processes and inhibiting tumor suppressor genes. With considerable potential in both haematological malignancies and solid tumors, histone deacetylase (HDAC) inhibitors have become an attractive epigenetic regulator in cancer treatment. This comprehensive study examines the molecular diversity of HDAC inhibitors across different cancer types, utilizing DNA methylation, histone modification, and miRNA regulation, thereby highlighting their role in altering epigenetic landscapes. The study investigates the differential efficacy between hematological tumors, where therapeutic applications are well-established, and solid tumors, where pharmacokinetic limitations still exist. The review examines new developments in combination therapy and their effects on the tumour microenvironment, particularly on the synergistic effects of HDAC inhibitors with targeted medicines and immunotherapeutics. It also discusses new therapeutic approaches based on selective HDAC inhibitors targeting specific isoforms, such as HDAC6 and HDAC11, in metabolically active tumors. Resistance mechanisms, biomarker-driven patient selection, and improvement of solid tumour delivery systems remain significant challenges. With expert perspectives on future developments, this study concludes by highlighting the need for the development of more selective inhibitors with improved pharmacokinetic properties and the optimization of combination methods for personalized cancer treatment approaches.