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Published on: October 2, 2014
Breast cancer and HSP90 inhibitors: is there a role beyond the HER2-positive subtype?
Leticia De Mattos-Arruda1, Javier Cortes
1Medical Oncology Department, Vall D'Hebron University Hospital, Paseo Vall d'Hebron 119-129, 08035 Barcelona, Spain. ldmattos@ir.vhebron.net
Abstract:
HSP90 inhibitors have shown great promise as therapeutic targets because they have the potential to suppress multiple signaling pathways simultaneously, and many are currently under clinical development. Because HER2 is known to be a client protein sensitive to inhibition of the HSP90 chaperone complex, HSP90 inhibitors have been studied in HER2-positive breast cancer and have shown promising results. In this article, we revisit HSP90 inhibitors in the context of breast cancer and discuss some notable preclinical data that reveal potential roles in both hormonal receptor-positive and triple negative breast tumor subtypes.
Insights
Heat shock protein 90 (HSP90) inhibitors show promise for breast cancer therapy by targeting multiple pathways. Preclinical data suggest HSP90 inhibitors may benefit hormonal receptor-positive and triple-negative breast cancer subtypes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Heat shock protein 90 (HSP90) is a molecular chaperone crucial for the stability of numerous client proteins.
- Inhibition of HSP90 disrupts the function of oncoproteins, making it a promising therapeutic strategy in cancer.
- HER2-positive breast cancer has shown sensitivity to HSP90 inhibition, with several agents in clinical development.
Purpose of the Study:
- To review the therapeutic potential of HSP90 inhibitors in various breast cancer subtypes.
- To discuss preclinical findings supporting HSP90 inhibition beyond HER2-positive disease.
- To highlight the role of HSP90 in hormonal receptor-positive and triple-negative breast cancers.
Main Methods:
- Literature review of preclinical studies on HSP90 inhibitors in breast cancer models.
- Analysis of data on HSP90 client proteins in different breast cancer subtypes.
- Discussion of clinical development status of HSP90 inhibitors.
Main Results:
- HSP90 inhibitors demonstrate broad potential by simultaneously suppressing multiple oncogenic signaling pathways.
- Preclinical studies indicate efficacy in HER2-positive breast cancer due to HER2's dependence on HSP90.
- Emerging data suggest potential therapeutic roles in hormonal receptor-positive and triple-negative breast cancer subtypes.
Conclusions:
- HSP90 inhibitors represent a versatile therapeutic approach for breast cancer, targeting key oncogenic drivers.
- Further investigation into HSP90 inhibitors is warranted for hormonal receptor-positive and triple-negative breast cancer.
- The simultaneous targeting of multiple pathways by HSP90 inhibitors offers a promising strategy for overcoming treatment resistance.
