HDACs and HDAC Inhibitors in Cancer Development and Therapy HDACs (histone deacetylases) regulate gene expression by deacetylating histones and non-histone proteins, influencing cancer development and progression. HDAC inhibitors (HDACi) are emerging as promising cancer therapies. HDACs are divided into four classes, with 18 human HDACs involved in various cancers. Aberrant HDAC expression is linked to malignancies, and HDAC inhibition can restore normal gene expression and function, inducing cell cycle arrest, apoptosis, and inhibition of angiogenesis and metastasis. HDACs also regulate DNA damage response, metastasis, and autophagy. HDACi have shown antitumor effects by modulating these processes. Clinical trials have approved several HDACi, including vorinostat, romidepsin, belinostat, and panobinostat, for treating hematological malignancies. However, their efficacy in solid tumors is limited due to pharmacokinetic issues and toxicity. Selective HDACi and combination therapies are being explored to improve therapeutic outcomes. HDACi may also target specific pathways, such as the PI3K pathway, and are being developed as dual-action agents. Overall, HDACs are critical in cancer biology, and HDACi offer potential therapeutic strategies for cancer treatment.HDACs and HDAC Inhibitors in Cancer Development and Therapy HDACs (histone deacetylases) regulate gene expression by deacetylating histones and non-histone proteins, influencing cancer development and progression. HDAC inhibitors (HDACi) are emerging as promising cancer therapies. HDACs are divided into four classes, with 18 human HDACs involved in various cancers. Aberrant HDAC expression is linked to malignancies, and HDAC inhibition can restore normal gene expression and function, inducing cell cycle arrest, apoptosis, and inhibition of angiogenesis and metastasis. HDACs also regulate DNA damage response, metastasis, and autophagy. HDACi have shown antitumor effects by modulating these processes. Clinical trials have approved several HDACi, including vorinostat, romidepsin, belinostat, and panobinostat, for treating hematological malignancies. However, their efficacy in solid tumors is limited due to pharmacokinetic issues and toxicity. Selective HDACi and combination therapies are being explored to improve therapeutic outcomes. HDACi may also target specific pathways, such as the PI3K pathway, and are being developed as dual-action agents. Overall, HDACs are critical in cancer biology, and HDACi offer potential therapeutic strategies for cancer treatment.