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On the Design of Combination Cancer Therapy

James H Doroshow1, Richard M Simon2

  • 1Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD, USA; Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.

Cell
|December 16, 2017
PubMed

Insights

Combination cancer therapy shows limited clinical synergy. Studies suggest that even successful treatments often work through individual drug effects, not combined interactions, challenging current approaches to cancer drug development.

Area of Science:

  • Oncology
  • Pharmacology
  • Translational Medicine

Background:

  • Combination therapy is standard for treating human malignancies.
  • Synergistic drug interactions are sought to improve treatment efficacy.

Purpose of the Study:

  • To evaluate the clinical translation of synergistic anticancer drug interactions observed in vitro.
  • To determine if combination therapy success is due to synergy or independent drug action.

Main Methods:

  • Analysis of cell culture data for synergistic drug interactions.
  • Review of results from mouse models and human clinical trials of combination therapies.

Main Results:

  • In vitro synergistic drug interactions rarely translate to clinical efficacy.
  • Successful combination therapies are often explained by the additive effects of individual drugs.
  • Clinical outcomes do not consistently support in vitro synergy findings.

Conclusions:

  • The clinical relevance of in vitro synergistic anticancer drug interactions is questionable.
  • Independent drug activities are a more likely explanation for successful combination therapies.
  • Rethinking preclinical models and clinical trial analysis for combination cancer treatments is warranted.

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