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Epigenetic Regulation of Differentially Expressed Drug-Metabolizing Enzymes in Cancer

Jiaqi Wang1, Lushan Yu1, Huidi Jiang1

  • 1Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China (J.W., L.Y., H.J., S.Z.) and Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, China (X.Z.).

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|July 1, 2020
PubMed

Insights

Aberrant expression of drug-metabolizing enzymes (DMEs) in cancer is linked to epigenetic changes. Understanding this connection aids in developing targeted cancer therapies and biomarkers.

Area of Science:

  • Biochemistry
  • Oncology
  • Epigenetics

Background:

  • Drug metabolism, crucial for drug efficacy and toxicity, involves phase I and phase II drug-metabolizing enzymes (DMEs).
  • Aberrant DME expression is implicated in cancer development and influences individual responses to chemotherapy.
  • Epigenetic mechanisms, beyond genetic factors, significantly regulate DME expression in cancer.

Purpose of the Study:

  • To review differentially expressed DMEs in various cancers.
  • To summarize the epigenetic modifications (DNA methylation, histone modification, noncoding RNAs) affecting DME expression in cancer.
  • To highlight the potential of targeting DME epigenetic regulation for cancer diagnosis, treatment, and prognosis.

Main Methods:

  • Literature review of studies on DME expression in cancer.
  • Analysis of epigenetic alterations impacting DME genes.
  • Synthesis of findings on the role of DMEs in cancer progression and chemoresistance.

Main Results:

  • Significant alterations in DME expression are observed across different cancer types.
  • Epigenetic mechanisms like DNA methylation, histone modifications, and noncoding RNAs are key regulators of these aberrant DME expressions.
  • These epigenetic changes in DMEs contribute to cancer development and influence patient response to anticancer drugs.

Conclusions:

  • Epigenetic regulation plays a critical role in the aberrant expression of DMEs in cancer.
  • Understanding these epigenetic mechanisms offers a foundation for personalized medicine and rational drug use in oncology.
  • Targeting epigenetic regulation of DMEs presents opportunities for novel cancer biomarkers and therapeutic strategies.

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