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Updated: Dec 23, 2025

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

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Exploiting evolutionary steering to induce collateral drug sensitivity in cancer

Ahmet Acar1,2, Daniel Nichol1, Javier Fernandez-Mateos1

  • 1Evolutionary Genomics and Modelling Lab, Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.

Nature Communications
|April 23, 2020
PubMed

Insights

Cancer drug resistance can be overcome by exploiting evolutionary trade-offs. This study demonstrates a novel experimental approach for

Area of Science:

  • Oncology
  • Evolutionary Biology
  • Computational Biology

Background:

  • Drug resistance mediated by clonal evolution is a major challenge in cancer therapy.
  • Evolutionary trade-offs, where resistance to one drug increases sensitivity to another, offer potential therapeutic targets.
  • Experimental recapitulation of cancer evolutionary dynamics is difficult.

Purpose of the Study:

  • To develop and demonstrate an experimental approach for 'evolutionary steering' to control tumor evolution and delay drug resistance.
  • To investigate the mechanisms underlying evolved drug sensitivity.

Main Methods:

  • Utilized single-cell barcoding for tracking cancer clones.
  • Grew large cell populations (10^8-10^9) without re-plating to mimic in vivo conditions.
  • Employed longitudinal, non-destructive monitoring of cancer clones.
  • Integrated mathematical modeling of tumor evolution.

Main Results:

  • Successfully demonstrated evolutionary steering in a lung cancer model.
  • Showed that evolutionary steering favorably shifted tumor clonal composition.
  • Observed collateral sensitivity and proliferative costs in evolved cancer clones.
  • Identified genomic mechanisms driving evolved sensitivity.

Conclusions:

  • The developed approach enables experimental modeling of evolutionary steering strategies.
  • This method has the potential to control treatment resistance in cancer therapy.
  • Understanding evolutionary trade-offs is crucial for developing effective cancer treatments.

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