articleCancer DiscoveryJan 4, 2022GREEN OA

Independent Drug Action in Combination Therapy: Implications for Precision Oncology

DPDeborah PlanaACAdam C. PalmerPKPeter K. Sorger

Harvard–MIT Division of Health Sciences and Technology · Center for Systems Biology · +1 more institution

PubMed
Indexed incrossrefpubmed

Abstract

Combination therapies are superior to monotherapy for many cancers. This advantage was historically ascribed to the ability of combinations to address tumor heterogeneity, but synergistic interaction is now a common explanation as well as a design criterion for new combinations. We review evidence that independent drug action, described in 1961, explains the efficacy of many practice-changing combination therapies: it provides populations of patients with heterogeneous drug sensitivities multiple chances of benefit from at least one drug. Understanding response heterogeneity could reveal predictive or pharmacodynamic biomarkers for more precise use of existing drugs and realize the benefits of additivity or…

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293
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Authors

3
  • DP
    Deborah PlanaCorresponding

    Harvard–MIT Division of Health Sciences and Technology, Center for Systems Biology

  • AC
    Adam C. Palmer

    University of North Carolina at Chapel Hill

  • PK
    Peter K. Sorger

    Center for Systems Biology

Topics & keywords

Keywords
  • Drug
  • Precision medicine
  • Drug response
  • Drug action
  • Precision oncology
  • Action (physics)
  • Clinical trial
  • Cancer drugs
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