Title:The Role of DNA Methylation in the Pathogenesis and Treatment of Cancer
Volume: 7
Issue: 4
Author(s): Jacob Peedicayil
Affiliation:
Keywords:
DNA, cancer, methylation, pathogenesis, treatment, Hypomethylation, Cancer Genome, Tumour, Focal Hypermethylation, Chemotherapy.
Abstract: DNA methylation is a major epigenetic mechanism that leads to inhibition of gene transcription and is known
to be involved in the pathogenesis of cancer. The effectors of DNA methylation are DNA methyltransferases (DNMTs)
that catalyze either de novo or maintenance methylation of hemimethylated DNA after DNA replication. DNA
methylation patterns in cancer are distorted, with three ways by which DNA methylation contributes to cancer:
hypomethylation of the cancer genome, focal hypermethylation of the promoters of tumour suppressor genes, and direct
mutagenesis. Drugs that inhibit DNMTs are proving to be useful in the treatment of cancer with a few such drugs
approved for clinical use. These drugs include nucleoside inhibitors, non-nucleoside inhibitors, oligonucleotides, and
noncoding RNAs that target messenger RNAs of genes encoding DNMTs. The major value of DNMT inhibitors could be
that at low doses they can induce the re-expression of aberrantly silenced tumour suppressor genes, allowing cancer cells
to revert to a normal phenotype and/or reacquire cellular pathways needed for cell cycle regulation and apoptosis
induction. They could also be useful in combination with other anticancer drugs.
