HDAC INHIBITORS: A NEW ARMOUR IN ANTI-CANCER THERAPEUTICS Download PDF

Histone deacetylase inhibitors (HDACi) are one of the new anti-cancer agents and in fact vorinostat has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. Several classes of HDACi have been identified including organic hydroxamic acids like TSA and SAHA, Short-chain fatty acids like butyrates and valproic acid, benzamides like MS-275, cyclic tetrapeptides like trapoxin and sulfonamide anilides and others. Histone deacetylase inhibitors (HDACi) de-repress genes that results in growth inhibition, differentiation and apoptosis of cancer cells. Vorinostat (SAHA), romidepsin (depsipeptide, FK-228), belinostat (PXD101) and LAQ824 have confirmed therapeutic benefits in cutaneous T-cell lymphoma (CTCL) without combination therapy and have also demonstrated some therapeutic benefit in other malignancies. Beyond cancer, there may be several novel therapeutic areas where HDACi may provide therapeutic benefits like in Inflammation, Polycythemia vera, essential Thrombocythemia, Myelofibrosis and Neurodegenerative diseases such as Alzheimer’s disease and Huntington’s disease. Belinostat appears to be promising for treating low malignant potential ovarian tumor. The combination of azacitidine, valproic acid, and all trans-retinoic acid has significant clinical activity in leukemia. Epigenetic agents in combination regimens for cancer therapy are being actively studied.