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Updated: Mar 6, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Published on: December 9, 2015

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Molecular mechanisms of therapy resistance in solid tumors: chasing "moving" targets

Laura J Tafe1

  • 1One Medical Center Drive, Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03754, USA. Laura.J.Tafe@hitchcock.org.

Virchows Archiv : an International Journal of Pathology
|March 11, 2017
PubMed

Insights

Personalized cancer therapies often fail due to acquired resistance. This review explores diverse resistance mechanisms to targeted treatments in lung, breast, prostate cancers, and melanoma, and strategies to overcome them.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • Personalized cancer therapy aims to target genomic aberrations driving tumor growth.
  • Acquired resistance to targeted therapies leads to disease progression in most patients within a year.

Purpose of the Study:

  • To review heterogeneous mechanisms of therapy resistance to tyrosine kinase inhibitors, endocrine/hormone therapy, and checkpoint blockade.
  • To discuss testing for resistance mechanisms and therapeutic strategies to overcome resistance.

Main Methods:

  • Literature review of resistance mechanisms in non-small cell lung cancer, breast cancer, castration-resistant prostate cancer, and melanoma.
  • Analysis of therapeutic approaches to overcome acquired resistance.

Main Results:

  • Tyrosine kinase inhibitors, endocrine/hormone therapy, and checkpoint blockade are subject to diverse resistance mechanisms.
  • Non-small cell lung cancer, breast cancer, castration-resistant prostate cancer, and melanoma serve as models for studying resistance.

Conclusions:

  • Understanding diverse resistance mechanisms is crucial for effective personalized cancer therapy.
  • Developing strategies to overcome resistance is essential for improving long-term patient outcomes.
Keywords:
Breast cancerCastration-resistant prostate cancerCheckpoint inhibitorsDrug resistanceEGFR T790MESR1 mutationEpithelial-mesenchymal transitionNon-small cell lung cancerResistance mechanismsSmall cell transformationTKI resistance

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