Modulation of Tumor Suppressor Genes by Histone Deacetylase Inhibitors in Cancer Therapy

Histone deacetylase (HDAC) inhibitors have emerged as promising therapeutics for various cancers due to their ability to modulate gene expression profiles and restore normal cellular functions. Among the key targets of HDAC inhibitors are tumor suppressor genes, which play crucial roles in regulating cell cycle progression, apoptosis, and DNA repair. However, despite their therapeutic potential, HDAC inhibitors come with significant drawbacks. These include off-target effects that can lead to unintended alterations in gene expression, toxicity to normal cells, and the development of drug resistance in some cancer patients. Additionally, the non-specific nature of some HDAC inhibitors can result in side effects such as fatigue, gastrointestinal disturbances, and hematological toxicity, limiting their clinical utility. This review provides a comprehensive overview of the impact of HDAC inhibitors on tumor suppressor genes in cancer therapy. We discussed the mechanisms by which HDAC inhibitors regulate the expression of tumor suppressor genes, including p53, p21, BRCA1, PTEN, and others, through histone hyperacetylation and chromatin remodeling. Furthermore, we described the therapeutic implications of HDAC inhibitor-induced modulation of tumor suppressor genes in various cancer types, highlighting the potential for combination therapies and personalized treatment approaches. Understanding the interplay between HDAC inhibitors and tumor suppressor genes is critical for optimizing the efficacy of HDAC inhibitor-based therapies and advancing precision medicine in oncology.