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A view on drug resistance in cancer

Author

Listed:
  • Neil Vasan

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • José Baselga

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College
    AstraZeneca)

  • David M. Hyman

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

Abstract

The problem of resistance to therapy in cancer is multifaceted. Here we take a reductionist approach to define and separate the key determinants of drug resistance, which include tumour burden and growth kinetics; tumour heterogeneity; physical barriers; the immune system and the microenvironment; undruggable cancer drivers; and the many consequences of applying therapeutic pressures. We propose four general solutions to drug resistance that are based on earlier detection of tumours permitting cancer interception; adaptive monitoring during therapy; the addition of novel drugs and improved pharmacological principles that result in deeper responses; and the identification of cancer cell dependencies by high-throughput synthetic lethality screens, integration of clinico-genomic data and computational modelling. These different approaches could eventually be synthesized for each tumour at any decision point and used to inform the choice of therapy.

Suggested Citation

  • Neil Vasan & José Baselga & David M. Hyman, 2019. "A view on drug resistance in cancer," Nature, Nature, vol. 575(7782), pages 299-309, November.
    • Handle: RePEc:nat:nature:v:575:y:2019:i:7782:d:10.1038_s41586-019-1730-1
    DOI: 10.1038/s41586-019-1730-1
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    6. Wei Xu & Sau Har Lee & Fengjun Qiu & Li Zhou & Xiaoling Wang & Tingjie Ye & Xudong Hu, 2021. "Association of SMAD4 loss with drug resistance in clinical cancer patients: A systematic meta-analysis," PLOS ONE, Public Library of Science, vol. 16(5), pages 1-14, May.
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    12. Heathcliff Dorado García & Fabian Pusch & Yi Bei & Jennifer Stebut & Glorymar Ibáñez & Kristina Guillan & Koshi Imami & Dennis Gürgen & Jana Rolff & Konstantin Helmsauer & Stephanie Meyer-Liesener & N, 2022. "Therapeutic targeting of ATR in alveolar rhabdomyosarcoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Rong Cai & Chiagoziem Ngwadom & Ravindra Saxena & Jayashree Soman & Chase Bruggeman & David P. Hickey & Rafael Verduzco & Caroline M. Ajo-Franklin, 2024. "Creation of a point-of-care therapeutics sensor using protein engineering, electrochemical sensing and electronic integration," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
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