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Combination therapies with HSP90 inhibitors against colorectal cancer

Kushtrim Kryeziu1, Jarle Bruun2, Tormod K Guren3

  • 1Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Colorectal Cancer Research Centre, Division for Cancer Medicine, Oslo University Hospital, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Biochimica Et Biophysica Acta. Reviews on Cancer
|February 2, 2019
PubMed

Insights

Heat shock protein 90 (HSP90) inhibition shows promise for colorectal cancer therapy. Combining HSP90 inhibitors with chemotherapy or immunotherapy may enhance antitumor effects, especially in specific subtypes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Heat shock protein 90 (HSP90) is vital for oncogene stability and cancer cell survival.
  • HSP90 is a validated therapeutic target in various cancers, including colorectal cancer.
  • Monotherapy with HSP90 inhibitors has shown limited clinical efficacy.

Purpose of the Study:

  • To explore the potential of HSP90 inhibitors in combination therapies for colorectal cancer.
  • To investigate biomarker-guided approaches and molecular subtype stratification for optimizing HSP90 inhibition.
  • To assess the immunomodulatory effects of HSP90 inhibition in cancer treatment.

Main Methods:

  • Review of preclinical and early-phase clinical studies on HSP90 inhibitors.
  • Analysis of synergistic effects with chemotherapy (5-fluorouracil) in mesenchymal colorectal cancer models.
  • Evaluation of HSP90 inhibition's role in enhancing anti-tumor immunity and response to immune checkpoint blockade.

Main Results:

  • Combination therapy with HSP90 inhibitors demonstrates improved antitumor activity compared to monotherapy.
  • Biomarker-guided strategies and stratification by consensus molecular subtypes may enhance efficacy.
  • HSP90 inhibition can potentially sensitize tumors to immunotherapy by modulating the tumor immune microenvironment.

Conclusions:

  • HSP90 inhibitors represent a promising therapeutic strategy for colorectal cancer, particularly in combination regimens.
  • Personalized approaches, including biomarker selection and molecular subtyping, are crucial for maximizing treatment benefits.
  • Targeting HSP90 may overcome resistance to chemotherapy and enhance responses to immune checkpoint blockade.
Keywords:
BiomarkerColorectal cancerCombination therapyHSP90Molecular stratification

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