Controlling Cancer By Epigenetics: Are We Ready for the Prime Time?

Epigenomics provides essential tools not only for therapeutic intervention but also as predictors of drug response. Unlike alterations in genetic components where the structure of a gene is changed (such as mutations, deletions, additions, single nucleotide polymorphism), epigenetics causes changes in gene expression without altering the genetic sequence. Furthermore, several epigenetic changes are reversible, and because of this, drugs have been developed that can reverse the epigenetic changes associated with different cancers. These epigenetic drugs target DNA methyltransferases, histone deacetylases and proteins associated with post-transcriptionally modified histones. Epigenetic regulators represent potential therapeutic targets as they often have binding domains that lend themselves well to small molecule inhibition. Resistance to cancer therapy is an ongoing challenge, and there is a need to seek out non-traditional approaches such as targeting epigenetic components for cancer therapy. Factors that contribute to the development of resistance to targeted therapy and how epigenetic regulators can be utilized to overcome this resistance will be discussed. Examples of several cancer types will be presented for which conventional targeted therapy has limited effects, but improved treatment outcomes are observed following epigenetic reprogramming of gene expression patterns, including modification of histones and DNA. Results from clinical trials have indicated the effectiveness of epigenetic drugs as cancer therapy, mainly when administered in combination with traditional anticancer drugs. These promising data suggest that epigenetic drugs have great potential in controlling and treating cancer.