Combination therapies with HSP90 inhibitors against colorectal cancer

Biochim Biophys Acta Rev Cancer. 2019 Apr;1871(2):240-247. doi: 10.1016/j.bbcan.2019.01.002. Epub 2019 Jan 30.


Oncogene stability and homeostasis mediated by the HSP90 chaperone is a crucial protection trait of cancer cells. Therefore, HSP90 represents an attractive therapeutic target for many cancers, including colorectal cancer. Although monotherapy has limited clinical efficacy, preclinical and early-phase clinical studies indicate improved antitumor activity when HSP90 inhibitors are combined with chemotherapies or targeted agents. This may be further improved with a biomarker-guided approach based on oncogenic HSP90 clients, or stratification based on the consensus molecular subtypes of colorectal cancer, suggesting a synergistic activity with 5-fluorouracil in preclinical models of the chemorefractory mesenchymal subtype. Furthermore, HSP90 inhibition may activate mechanisms to turn non-immunogenic tumors hot and improve their recognition by the immune system, suggesting synergy with immune checkpoint blockade.

Keywords: Biomarker; Colorectal cancer; Combination therapy; HSP90; Molecular stratification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans


  • HSP90 Heat-Shock Proteins