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Contributions of co-chaperones and post-translational modifications towards Hsp90 drug sensitivity

Annerleim Walton-Diaz1, Sahar Khan, Dimitra Bourboulia

  • 1Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1107, USA.

Future Medicinal Chemistry
|June 6, 2013
PubMed

Insights

Heat shock protein 90 (Hsp90) is a key cancer target. This review examines how co-chaperones and post-translational modifications affect Hsp90 inhibitor efficacy in cancer treatment.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Heat shock protein 90 (Hsp90) is a molecular chaperone crucial for stabilizing oncoproteins driving cancer progression.
  • Hsp90 is a validated therapeutic target for various cancers, including non-small-cell lung cancer and HER2-positive breast cancer.
  • Hsp90's function relies on ATP binding and hydrolysis, making its ATPase activity a key target for inhibitors.

Purpose of the Study:

  • To review the regulatory roles of co-chaperones and post-translational modifications (PTMs) on Hsp90.
  • To analyze how these regulatory factors influence the effectiveness of Hsp90 inhibitors in cancer therapy.

Main Methods:

  • Literature review of studies investigating Hsp90 regulation.
  • Analysis of research on Hsp90 inhibitors and their mechanisms of action.
  • Synthesis of data on the interplay between Hsp90, co-chaperones, PTMs, and drug efficacy.

Main Results:

  • Co-chaperones and PTMs significantly modulate Hsp90's ATPase activity and client protein interactions.
  • These regulatory mechanisms can impact the sensitivity and resistance of cancer cells to Hsp90 inhibitors.
  • Understanding these modulations is critical for optimizing Hsp90-targeted cancer therapies.

Conclusions:

  • Hsp90 inhibitors represent a promising therapeutic strategy for cancer treatment.
  • The efficacy of Hsp90 inhibitors is influenced by cellular factors including co-chaperones and PTMs.
  • Further research into these regulatory networks will be essential for developing more effective Hsp90-targeted drugs.

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