Epigenetic reprogramming and potential application of epigenetic-modifying drugs in acquired chemotherapeutic resistance

Logeswari Ponnusamy, Prathap Kumar S. Mahalingaiah, Kamaleshwar P. Singh

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Chemotherapy is the most common clinical choice of treatment for cancer, however, acquired chemoresistance is a major challenge that limits the successful outcome of this option. Systematic review of in vitro, in vivo, preclinical and clinical studies suggests that acquired chemoresistance is polygenic, progressive, and involve both genetic and epigenetic heterogeneities and perturbations. Various mechanisms that confer resistance to chemotherapy are tightly controlled by epigenetic regulations. Poised epigenetic plasticity and temporal increase in epigenetic alterations upon chemotherapy make chemoresistance likely an epigenetic-driven process. The transient and reversible nature of epigenetic modulations enable ways to intervene the epigenetic re-programing associated with acquired chemoresistance via application of epigenetic modifying drugs. This review discusses recent understandings behind the various mechanisms of acquired chemoresistance that are under the control of epigenetic drivers, potential application of epigenetic-based drugs in resensitizing refractory cancers to chemotherapy, the limitations and future scope for clinical application of epigenetic therapeutics in successfully addressing chemoresistance.

Original languageEnglish
Title of host publicationAdvances in Clinical Chemistry
EditorsGregory S. Makowski
PublisherAcademic Press Inc.
Pages219-259
Number of pages41
ISBN (Print)9780128208014
DOIs
StatePublished - 2020

Publication series

NameAdvances in Clinical Chemistry
Volume94
ISSN (Print)0065-2423
ISSN (Electronic)2162-9471

Keywords

  • Cellular reprogramming
  • Chemoresistance
  • DNA methylation
  • DNA repair
  • EpiDrugs
  • Epigenetics
  • Histone modifications

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  • Cite this

    Ponnusamy, L., Mahalingaiah, P. K. S., & Singh, K. P. (2020). Epigenetic reprogramming and potential application of epigenetic-modifying drugs in acquired chemotherapeutic resistance. In G. S. Makowski (Ed.), Advances in Clinical Chemistry (pp. 219-259). (Advances in Clinical Chemistry; Vol. 94). Academic Press Inc.. https://doi.org/10.1016/bs.acc.2019.07.011