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Blocking the survival of the nastiest by HSP90 inhibition

Paul Workman1, Paul A Clarke1, Bissan Al-Lazikani1

  • 1Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.

Oncotarget
|January 29, 2016
PubMed

Insights

Cancer cells evolve resistance to targeted therapies due to genetic and epigenetic heterogeneity. Inhibiting HSP90 molecular chaperone alongside targeted drugs can restrain this drug resistance evolution.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer genetic, epigenetic, and phenotypic heterogeneity drives therapeutic resistance.
  • Emergence of resistant clones under drug treatment poses a significant challenge to molecularly targeted therapy.
  • Darwinian selective pressure contributes to the development of drug resistance in cancer.

Purpose of the Study:

  • To investigate strategies for restraining the evolution of drug resistance in cancer.
  • To evaluate the efficacy of co-administering HSP90 inhibitors with molecularly targeted therapies.

Main Methods:

  • Utilized pharmacologic inhibitors targeting the HSP90 molecular chaperone.
  • Co-administered HSP90 inhibitors with existing molecularly targeted therapies in cancer models.
  • Assessed the impact on the emergence and evolution of drug-resistant clones.

Main Results:

  • Co-administration of HSP90 inhibitors significantly restrained the evolution of drug resistance.
  • HSP90 inhibition proved effective in counteracting the emergence of resistant clones under selective pressure.
  • Demonstrated a viable strategy to overcome therapeutic resistance in heterogeneous cancers.

Conclusions:

  • Targeting the HSP90 molecular chaperone is a promising strategy to overcome therapeutic resistance in heterogeneous cancers.
  • Combined inhibition of HSP90 and targeted therapy can prevent the emergence of resistant clones.
  • This approach offers a potential solution to enhance the efficacy of molecularly targeted cancer treatments.
Keywords:
HSP90

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