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Tolerant/Persister Cancer Cells and the Path to Resistance to Targeted Therapy

Mirna Swayden1,2, Houssein Chhouri1,2, Youssef Anouar1,2

  • 1Laboratoire Différenciation et Communication Neuronale et Neuroendocrine, UNIROUEN, INSERM, Normandie Université, 76183 Rouen, France.

Cells
|December 9, 2020
PubMed

Insights

Cancer can resist targeted therapies not just through mutations, but also via non-genetic mechanisms. Tolerant cancer cells survive treatment by altering gene expression and cell communication, leading to therapy resistance.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Therapeutics

Background:

  • Cancer's ability to adapt and evolve poses a significant challenge to targeted therapies.
  • While genetic mutations are known drivers of resistance, non-genetic mechanisms are increasingly recognized.

Purpose of the Study:

  • To review non-genetic mechanisms of cancer resistance to targeted therapies.
  • To highlight the role of gene expression changes in therapy resistance.

Main Methods:

  • Literature review of recent findings on cancer resistance.
  • Focus on non-genetic adaptive mechanisms.
  • Analysis of gene expression alterations.

Main Results:

  • Cancer resistance can emerge from tolerant/persister cell subpopulations.
  • Mechanisms include pathway rebound, transcriptional rewiring, and cell communication.
  • Changes in gene expression are central to these non-genetic resistance pathways.

Conclusions:

  • Non-genetic mechanisms, particularly those altering gene expression, are critical for cancer resistance to targeted therapies.
  • Understanding these pathways is essential for developing more effective cancer treatments.
Keywords:
BRAFEGFRcell signalingdrug resistanceintratumor heterogeneitylung cancermelanomatargeted therapytolerant and persister cells

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