Abstract
The molecular chaperone heat shock protein 90 (HSP90) regulates multiple crucial signalling pathways in cancer by driving the maturation of key signalling components, thereby playing a crucial role in tumorigenesis and drug resistance in cancer. Inhibition of HSP90 results in metastable conformational collapse of its client proteins and their proteasomal degradation. Considerable efforts have been devoted to the development of small-molecule inhibitors targeting HSP90, and more than 20 inhibitors have been evaluated in clinical trials for cancer therapy. However, owing to disadvantages such as organ toxicity and drug resistance, only one HSP90 inhibitor has been approved for use in clinical settings. In recent years, HSP90 inhibitors used in combination with other anti-cancer therapies have shown remarkable potential in the treatment of cancer. HSP90 inhibitors work synergistically with various anti-cancer therapies, including chemotherapy, targeted therapy, radiation therapy and immunotherapy. HSP90 inhibitors can improve the pharmacological effects of the above-mentioned therapies and reduce treatment resistance. This review provides an overview of the use of combination therapy with HSP90 inhibitors and other anti-cancer therapies in clinical and preclinical studies reported in the past decade and summarises design strategies and prospects for these combination therapies. Altogether, this review provides a theoretical basis for further research and application of these combination therapies in the treatment of cancer.
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References
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Acknowledgements
This work is funded by the National Key Research and Development Program [Grant No. 2017YFC1702006], the Natural Science Foundation of Liaoning Province of China [Grant No. 2020-MS-105], and the Fundamental Research Funds for the Central Universities [Grant No. DUT22YG111].
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Yajun Liu and Chenyao Li prepared the original manuscript; Yajun Liu and Shutao Tan revised the manuscript. Yajun Liu, Shutao Tan and Hongwei Liu conceived the manuscript and polished writing.
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Liu, Y., Li, C., Liu, H. et al. Combination therapy involving HSP90 inhibitors for combating cancer: an overview of clinical and preclinical progress. Arch. Pharm. Res. (2024). https://doi.org/10.1007/s12272-024-01494-1
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DOI: https://doi.org/10.1007/s12272-024-01494-1