Epigenetic Targets in Cancer Therapy: A Pharmacological Review of Histone Modifiers and DNA Methylation Inhibitors

Abstract

Cancer is a multifactorial and complex disease, and it is hereditary as well as epigenomically modified. A permanent change in the code of the DNA on the other, is genetic mutation, but a control of gene expression, without altering the genetic code upon which it is based, is called an epigenetic modification. Chromatin structure and gene transcription regulation modification of DNA methylation and histone play a significant role in preserving normal cell identity and cell functions. The epigenetic changes are not permanent and, in contrast to the genetic mutations that are generally irreversible, they can be reversible, and there is only one possibility of a curative intervention. That has resulted in the development of epigenetic drugs that regulate the activity of important enzymes that write, read or erase epigenetic marks. Histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), histone demethylases and DNA methyltransferases (DNMTs). FDA approved epigenetic therapies (mostly against hematologic malignancies, although many more have been in preclinical and clinical trials against hematologic and solid tumors) already exist and nowadays there are many more in preclinical and clinical trials against hematologic and solid tumors. It also talks about clinical possibility of approved epigenetic drugs approved so far, new therapeutic transactions and combination. And, lastly, we consider general problems like resistance to drugs, off-target effects and predictive biomarkers and guidelines on how to improve the accuracy and efficacy of epigenetic therapy in cancer.