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Updated: Mar 25, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

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Cancer Drug Resistance: A Brief Overview from a Genetic Viewpoint

José Rueff1, António Sebastião Rodrigues2

  • 1Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana 6, 1150-008, Lisbon, Portugal. jose.rueff@fcm.unl.pt.

Methods in Molecular Biology (Clifton, N.J.)
|February 25, 2016
PubMed

Insights

Cancer drug resistance, a major cause of treatment failure in over 90% of metastatic cancers, arises from intrinsic or acquired tumor mechanisms. Understanding these diverse resistance pathways is crucial for developing effective cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cancer drug resistance significantly contributes to therapeutic failure in numerous cancers, affecting over 90% of patients with metastatic disease.
  • Resistance can be intrinsic, based on patient genetics, or acquired by tumors initially sensitive to treatment.

Purpose of the Study:

  • To review the multifaceted mechanisms underlying cancer drug resistance, with a focus on acquired resistance.
  • To highlight the role of tumor micro-heterogeneity in driving therapeutic failure.

Main Methods:

  • Literature review of established and emerging mechanisms of cancer drug resistance.
  • Analysis of genetic and epigenetic factors contributing to treatment failure.

Main Results:

  • Acquired resistance often stems from tumor micro-clonality and genetic heterogeneity.
  • Key mechanisms include altered drug transporter expression, impaired DNA repair and apoptosis, epigenetic modifications (methylation, acetylation, microRNAs), drug target mutations, cell cycle dysregulation, and the tumor microenvironment.

Conclusions:

  • Cancer drug resistance is a complex, multifactorial phenomenon.
  • Addressing tumor heterogeneity and diverse resistance mechanisms is essential for improving cancer treatment outcomes.
Keywords:
Acquired resistance and adaptive compensatory pathwaysAcquired resistance and tumor micro-heterogeneityDNA repair and resistanceEpigenomics and resistanceIntrinsic resistance and pharmacogeneticsTumor microenvironment and resistanceUptake and efflux transporters in resistance

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