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Resistance to platinum-based cancer drugs: a special focus on epigenetic mechanisms

Yuselin Mora1, María Elena Reyes1,2, Louise Zanella1

  • 1Laboratory of Integrative Biology (LIBi), Scientific & Technological Bioresource Nucleus- Center for Excellence in Translational Medicine (BIOREN-CEMT), Universidad de La Frontera, Temuco, 4810296, Chile.

Pharmacogenomics
|July 20, 2021
PubMed

Insights

Epigenetics, including DNA methylation and histone modification, drives chemoresistance in cancer, particularly to platinum drugs. Epigenetic therapies show promise in overcoming this resistance, enhancing platinum-based drug efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Chemoresistance significantly limits cancer treatment efficacy, especially with platinum-based drugs.
  • Epigenetic alterations play a crucial role in the development of cancer drug resistance.
  • Mechanisms include DNA methylation, histone modification, and noncoding RNAs affecting drug metabolism and cellular processes.

Purpose of the Study:

  • To review current findings on epigenetic regulation in platinum drug resistance in cancer.
  • To summarize clinical trials investigating epigenetic therapy for platinum resistance.
  • To evaluate the synergistic potential of epigenetic therapy with platinum-based drugs.

Main Methods:

  • Literature review of epigenetic mechanisms in platinum drug resistance.
  • Analysis of gene expression changes related to ADME and key cellular processes.
  • Survey of ongoing and completed clinical trials on epigenetic therapies.

Main Results:

  • Epigenetic modifications influence genes involved in drug absorption, distribution, metabolism, and excretion (ADME).
  • Epigenetic changes affect genes critical for cell proliferation, DNA repair, apoptosis, and signal transduction.
  • Clinical trials are exploring epigenetic agents to reverse or overcome chemoresistance.

Conclusions:

  • Epigenetic mechanisms are central to platinum drug resistance in various cancers.
  • Epigenetic therapies offer a promising strategy to enhance the effectiveness of platinum-based chemotherapy.
  • Further research and clinical evaluation are needed to optimize combination strategies.
Keywords:
ADME genecancerdrug resistanceepigeneticsnon-ADME geneplatinum-based drugs

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