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Treatment-Induced Mutagenesis and Selective Pressures Sculpt Cancer Evolution

Subramanian Venkatesan1,2, Charles Swanton1,2, Barry S Taylor3,4,5

  • 1UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, London WC1E 6BT, United Kingdom.

Cold Spring Harbor Perspectives in Medicine
|March 15, 2017
PubMed

Insights

Cancer evolves under therapy pressure, developing resistance through clonal evolution. This review details genetic mechanisms driving resistance to targeted therapies and chemotherapies.

Area of Science:

  • Oncology
  • Cancer Biology
  • Evolutionary Medicine

Background:

  • Cancer remains a major global health challenge, despite advances in understanding its molecular basis.
  • Tumor heterogeneity and therapeutic selective pressures complicate cancer eradication and control.
  • Understanding cancer evolution under treatment is crucial for improving therapeutic strategies.

Purpose of the Study:

  • To review patterns of clonal evolution in tumors during cancer therapy.
  • To focus on the genetic mechanisms underlying treatment resistance.
  • To explore resistance development against both targeted therapies and traditional chemotherapies.

Main Methods:

  • This is a review article, synthesizing existing research.
  • Analysis of published studies on cancer treatment resistance and clonal evolution.
  • Focus on genetic aberrations conferring resistance.

Main Results:

  • Intratumor heterogeneity and clonal evolution are linked to primary and acquired treatment resistance.
  • Resistance to targeted therapies often involves drug target mutation or pathway aberrations.
  • Recurrent genetic aberrations conferring resistance to chemotherapy are less understood due to mutagenic effects.

Conclusions:

  • Cancer treatment resistance is driven by evolutionary processes and genetic alterations.
  • Distinct mechanisms confer resistance to targeted therapies versus chemotherapies.
  • Further research is needed to fully elucidate chemotherapy resistance mechanisms.

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