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Updated: Oct 20, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Epigenetic Alterations and Mechanisms That Drive Resistance to Targeted Cancer Therapies

Narendra Wajapeyee1,2, Romi Gupta1,2

  • 1Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama. nwajapey@uab.edu romigup@uab.edu.

Cancer Research
|September 17, 2021
PubMed

Insights

Targeted cancer therapies show initial promise but drug resistance frequently emerges. Understanding epigenetic factors driving resistance is crucial for developing effective treatments for drug-resistant cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Cancer involves complex genetic and epigenetic alterations.
  • Targeted therapies based on driver oncogenes offer effective treatments for various cancers.
  • Therapeutic resistance is a significant clinical challenge.

Purpose of the Study:

  • To review mechanisms of resistance to targeted cancer therapeutics.
  • To highlight the role of epigenetic factors in driving drug resistance.
  • To discuss implications for preventing and treating drug-resistant cancers.

Main Methods:

  • Analysis of large-scale sequencing data from patient-derived cancer samples.
  • Review of studies identifying molecular alterations conferring resistance.
  • Elaboration on epigenetic factors and oncogenic pathways.

Main Results:

  • Targeted therapies can lead to robust initial responses but resistance often develops.
  • Mechanisms of resistance include alterations in transcriptome, transcription factors, DNA, and chromatin regulators.
  • Epigenetic alterations are key drivers of drug resistance and oncogenic pathways.

Conclusions:

  • Understanding resistance mechanisms is vital for overcoming therapeutic limitations.
  • Epigenetic modifications play a critical role in acquired drug resistance.
  • This knowledge has direct implications for developing novel strategies against drug-resistant cancers.

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