Role of histone demethylases and histone methyltransferases in triple-negative breast cancer: Epigenetic mnemonics

Triple-negative breast cancer (TNBC) is a particularly lethal subtype of breast cancer owing to its heterogeneity, high drug resistance, poor prognosis and lack of therapeutic targets. Recent insights into the complexity of TNBC have been explained by epigenetic regulation and its ability to modulate certain oncogenes and tumour suppressor genes. This has opened an emerging area in anti-cancer therapy using epigenetic modulating drugs, highlighting the epigenetic reprogramming during tumorigenesis and tumour development. Histone methylation and demethylation are such dynamic epigenetic mechanisms mediated by histone methyltransferases (HMTs) and histone demethylases (HDMs), respectively. The interplay between HMTs and HDMs in histone methylation extrapolates their viability as druggable epigenetic targets in TNBC. In this review, we aim to summarize recent progress in the field of epigenetics focusing on HMTs and HDMs in TNBC development and their potential use in targeted therapy for TNBC management. [Display omitted] •Histone methylation and demethylation have crucial role in TNBC development.•HDMs like KDM1A, KDM2B, KDM4A and KDM5A have an overall pro-tumorigenic action.•SMYD2, PRMT1 and PRMT5 are HMTs that promote methylation at non-histone substrates.•SETD1A, DOT1L, EZH2 and NSD2 methylate histones at their site specific positions.•Mutated KMT2D is an HMT regulating cancer dissemination and metastasis in TNBC.