Epidrugs: targeting epigenetic marks in cancer treatment

Abstract

Growing evidence suggests that aberrant epigenetic regulation of gene function is strongly related to the genesis of cancer. Unlike genetic mutations, the ability to reprogram the epigenetic landscape in the cancer epigenome is one of the most promising target therapies in both treatment and reversibility of drug resistance. Epigenetic alterations in cancer development and progression may be the basis for the individual variation in drug response. Thus, this review focuses on the emerging area of pharmaco(epi)genomics, specifically highlighting epigenetic reprogramming during tumorigenesis and how epigenetic markers are targeted as a therapy (epidrugs) and the clinical implications of this for cancer treatment.

Aberrant DNA Methylation of ABC Transporters in Cancer

“…Increasing evidence suggests that epigenetic modulators have the potential to revert epigenetic aberrations and thus to reprogram neoplastic cells toward a normal state [ 181 ]. Since epigenetic aberrations occur early and frequently during carcinogenesis, the use of epigenetic modulators, in combination with other therapies, is considered a promising strategy [ 181 , 182 , 183 ].…”

“…Increasing evidence suggests that DNMT inhibitors may have the potential to reactivate genes that have been silenced by DNA hypermethylation, e.g., tumor suppressor genes [ 186 ]. Both synthetic and natural DNMT inhibitors have already been tested in vitro and in vivo in combination with other therapies for a variety of cancer types [ 183 , 186 ], including multiple myeloma [ 184 ] and other hematological cancers [ 187 ]. Currently, only a few epigenetic modulators are used in clinical practice, mainly for treatment of hematological cancers [ 188 ].…”

Epidrug Repurposing: Discovering New Faces of Old Acquaintances in Cancer Therapy

“…In consequence, DNA hypomethylation at specific regions can activate the aberrant expression of genes, some of which could behave as proto-oncogenes (18). Finally, as aforementioned, alterations of hypermethylated patterns in repetitive sequences can promote the activation of transposable elements and chromosomal instability, both phenomena being also correlated with carcinogenesis and metastasis (6).…”

“…Nowadays, it is known that as cancer progresses, there are genetic aberrations that make tumors highly prone to developing resistance to therapies (5). Emerging data on cancer-associated epigenetic alterations have shown that epigenetic modifications leading to drug resistance may be the cue for individual variation in chemotherapy response, having the potential to be reversible using epigenetic therapy (6). The possibility to reprogram the cancer epigenome is becoming a promising target therapy for both, treatment development and reversibility of drug resistance.…”

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

“…The vorinostat, panobinostat, belinostat, and romidepsin are FDA-approved HDAC inhibitors (HDACi). These last drugs act by blocking the catalytic domain of HADCs and are associated with changes in the acetylation patterns of histones [143]. Although the undesirable off-target effects of epi-drugs still need to be overcome, accumulating findings pointed out that this therapy may reverse stem cell-like behavior and chemoresistance [144].…”