Targeting Epigenetic Regulators in Cancer to Overcome Resistance to Targeted Therapy

  • Mukesh VermaEmail author
  • Vineet KumarEmail author
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 20)


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. Epigenomics provides essential tools not only for therapeutic intervention but also as predictors of drug response. Unlike alteration of genetic components, where the structure of a gene is changed, such as mutations, deletions, additions, and single nucleotide polymorphisms, epigenetics changes gene expression without altering the genetic sequence. Furthermore, several epigenetic changes are reversible, and as a result, 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. Here, we discuss factors that contribute to the development of resistance to targeted therapy and how epigenetic regulators can be utilized to overcome this resistance. We provide examples of several cancer types 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 efficacy 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.


Biomarker Epigenetics Epidemiology Histones Methylation Treatment 



Area under curve


Cyclin-dependent kinase inhibitor 1


Colorectal cancer


Castration resistant prostate cancer


Cancer stem cells


DNA methyltransferases


Epithelial-to-mesenchymal transition


Enhancer of zeste homolog 2


Histone acetyltransferases


Hepatocellular carcinoma


Histone deacetylase


Human epidermal growth factor receptor


Hypericin-mediated photodynamic therapy


Histone lysine methyltransferases


Long interspersed nuclear elements


Micro RNAs


3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide


Non-small cell lung cancer


Oncogenic miRNAs


Overall response rate


Prostate-specific antigen


Renal cell carcinoma


Suberoylanilide hydroximic acid


Short interspersed nuclear elements


Ten-eleven translocation protein family


Trichostatin A


Vascular endothelial growth factor


Valproic acid


Financial Disclosure

There is no financial conflict.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Methods and Technologies Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population SciencesNational Cancer Institute, National Institutes of HealthBethesdaUSA
  2. 2.Department of PhysiologyNational University of SingaporeSingaporeSingapore

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