Epigenetic reprogramming in cancer: From diagnosis to treatment

Abstract

Disruption of the epigenetic program of gene expression is a hallmark of cancer that initiates and propagates tumorigenesis. Altered DNA methylation, histone modifications and ncRNAs expression are a feature of cancer cells. The dynamic epigenetic changes during oncogenic transformation are related to tumor heterogeneity, unlimited self-renewal and multi-lineage differentiation. This stem cell-like state or the aberrant reprogramming of cancer stem cells is the major challenge in treatment and drug resistance. Given the reversible nature of epigenetic modifications, the ability to restore the cancer epigenome through the inhibition of the epigenetic modifiers is a promising therapy for cancer treatment, either as a monotherapy or in combination with other anticancer therapies, including immunotherapies. Herein, we highlighted the main epigenetic alterations, their potential as a biomarker for early diagnosis and the epigenetic therapies approved for cancer treatment.

Associations of Heavy Metals with Cognitive Function: An Epigenome‐Wide View of DNA Methylation and Mediation Analysis

“…Epigenetic reprogramming, which leads to changes in the cell landscape, is emerging as a promising preventive or therapeutic strategy for diseases. 78,79 The inhibition of epigenetic modifications by certain compounds could attenuate the chemical-induced neurotoxic effects. 80 The present study's major strength is that we evaluated the potential functional consequence associated with arsenic-related DMPs, and the clear association with clinical phenotypes underscores the necessity for further development of such biomarkers.…”

Advances in Hodgkin Lymphoma Treatment: From Molecular Biology to Clinical Practice

“…Disruption of normal epigenetic regulation of gene expression is a hallmark of cancer and contributes to human tumor development and progression. As epigenetic changes are reversible, they represent a potential target for cancer therapy [125].…”

“…DNA methylation by DNA methyltransferase enzymes (DNMT) typically represses gene transcription. Thus, DNA hypermethylation may reduce the expression of key tumor suppressor genes in human cancers, and tumor cells in cHL have been found to be characterized by a high number of hypermethylated genes [125,126]. DNMT inhibitors (DNMTi) such as azacitidine and decitabine could reverse this aberrant epigenetic regulation and have already been shown to be effective on myelodysplastic syndromes and acute myeloid leukemia [127,128].…”

“…Epigenetic modification of histone proteins controls chromatin structure and, thus, gene expression. Histone deacetylases (HDACs) are enzymes that negatively regulate gene expression by removing acetyl groups from histones, causing chromatin condensation [125]. In cHL, overexpression of some specific isoforms of HDACs appears to correlate with shorter survival [134].…”

The bidirectional interplay between ncRNAs and methylation modifications in gastrointestinal tumors

“…Many studies have found that histone methylation plays a vital role in regulating ncRNA expression 48 . In esophageal cancer, EZH2, as a histone methyltransferase, promotes esophageal cancer cells' invasion and EMT process by upregulating miR-200c.…”