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Exploiting evolutionary steering to induce collateral drug sensitivity in cancer

Author

Listed:
  • Ahmet Acar

    (The Institute of Cancer Research
    Middle East Technical University)

  • Daniel Nichol

    (The Institute of Cancer Research)

  • Javier Fernandez-Mateos

    (The Institute of Cancer Research)

  • George D. Cresswell

    (The Institute of Cancer Research)

  • Iros Barozzi

    (Imperial College London)

  • Sung Pil Hong

    (Imperial College London)

  • Nicholas Trahearn

    (The Institute of Cancer Research)

  • Inmaculada Spiteri

    (The Institute of Cancer Research)

  • Mark Stubbs

    (The Institute of Cancer Research)

  • Rosemary Burke

    (The Institute of Cancer Research)

  • Adam Stewart

    (The Institute of Cancer Research)

  • Giulio Caravagna

    (The Institute of Cancer Research)

  • Benjamin Werner

    (The Institute of Cancer Research)

  • Georgios Vlachogiannis

    (The Institute of Cancer Research)

  • Carlo C. Maley

    (Arizona State University)

  • Luca Magnani

    (Imperial College London)

  • Nicola Valeri

    (The Institute of Cancer Research
    The Royal Marsden NHS Foundation Trust)

  • Udai Banerji

    (The Institute of Cancer Research
    The Institute of Cancer Research
    The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust)

  • Andrea Sottoriva

    (The Institute of Cancer Research)

Abstract

Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using ‘evolutionary steering’ to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 108–109 cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model, showing that it shifts the clonal composition of the tumour in our favour, leading to collateral sensitivity and proliferative costs. Genomic profiling revealed some of the mechanisms that drive evolved sensitivity. This approach allows modelling evolutionary steering strategies that can potentially control treatment resistance.

Suggested Citation

  • Ahmet Acar & Daniel Nichol & Javier Fernandez-Mateos & George D. Cresswell & Iros Barozzi & Sung Pil Hong & Nicholas Trahearn & Inmaculada Spiteri & Mark Stubbs & Rosemary Burke & Adam Stewart & Giuli, 2020. "Exploiting evolutionary steering to induce collateral drug sensitivity in cancer," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15596-z
    DOI: 10.1038/s41467-020-15596-z
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    Cited by:

    1. Benjamin Wölfl & Hedy te Rietmole & Monica Salvioli & Artem Kaznatcheev & Frank Thuijsman & Joel S. Brown & Boudewijn Burgering & Kateřina Staňková, 2022. "The Contribution of Evolutionary Game Theory to Understanding and Treating Cancer," Dynamic Games and Applications, Springer, vol. 12(2), pages 313-342, June.

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