Targeting cancer epigenetic pathways with small-molecule compounds: Therapeutic efficacy and combination therapies

Abstract

Epigenetics mainly refers to covalent modifications to DNA or histones without affecting genomes, which ultimately lead to phenotypic changes in cells or organisms. Given the abundance of regulatory targets in epigenetic pathways and their pivotal roles in tumorigenesis and drug resistance, the development of epigenetic drugs holds a great promise for the current cancer therapy. However, lack of potent, selective, and clinically tractable small-molecule compounds makes the strategy to target cancer epigenetic pathways still challenging. Therefore, this review focuses on epigenetic pathways, small molecule inhibitors targeting DNA methyltransferase (DNMT) and small molecule inhibitors targeting histone modification (the main regulatory targets are histone acetyltransferases (HAT), histone deacetylases (HDACs) and histone methyltransferases (HMTS)), as well as the combination strategies of the existing epigenetic therapeutic drugs and more new therapies to improve the efficacy, which will shed light on a new clue on discovery of more small-molecule drugs targeting cancer epigenetic pathways as promising strategies in the future.

Keywords: A-485 (PubChem CID: 118958122); AC1NOD4Q (PubChem CID: 5086250); ACY241 (PubChem CID: 53340426); CC-486 (PubChem CID: 9840076); Cancer therapy; Combination strategy; DNA methyltransferase; Entinostat (PubChem CID: 4261); Epigenetic drug; FL-411 (PubChem CID: 135567026); Histone modification; MC3343 (PubChem CID: 76318201); ORY-1001 (PubChem CID: 71664305); Romidepsin (PubChem CID: 5352062); Tenovin-6 (PubChem CID: 24772043).