HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review)

• Published in: Oncology reports Vol. 49; no. 1; p. 1
• Main Authors: Li, Zi-Nan, Luo, Ying
• Format: Journal Article
• Language: English
• Published: Athens Spandidos Publications 01.01.2023; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Adenosine triphosphatase; Binding sites; Breast cancer; Cancer; Cancer therapies; Cell cycle; Chemotherapy; Cytoplasm; Drug resistance; Endoplasmic reticulum; Health aspects; Heat shock proteins; Immunotherapy; Kinases; Medical prognosis; Metabolism; Proteins; Review; Signal transduction
• ISSN: 1021-335X; 1791-2431; 1791-2431
• DOI: 10.3892/or.2022.8443

Heat shock protein 90 (HSP90) is a vital chaperone protein, regulating signaling pathways and correcting misfolded proteins in cancer cells by interacting with oncogenic client proteins and co-chaperones. The inhibition of HSP90 chaperone machinery has been demonstrated as a potential approach with which to inhibit tumor survival, proliferation, invasion and migration. Numerous HSP90 inhibitors have been reported and have exhibited value as cancer-targeted therapies by interrupting the ATPase activity of HSP90, thus suppressing the oncogenic pathways in cancer cells. These inhibitors have been classified into three categories: i) N-terminal domain (NTD) inhibitors; ii) C-terminal domain (CTD) inhibitors; and iii) isoform-selective inhibitors. However, none of these HSP90 inhibitors are used as clinical treatments. The major limiting factors can be summarized into drug resistance, dose-limiting toxicity and poor pharmacokinetic profiles. Novel HSP90-targeted compounds are constantly being discovered and tested for their antitumor efficacy in preclinical and clinical trials, highlighting the prospect of the use of HSP90 inhibitors as cancer-targeted therapies. Additionally, improved antitumor effects have been observed when HSP90 inhibitors are used in combination with chemotherapy, targeted agents, or immunotherapy. In the present review, the effects of HSP90 inhibitors on the management of the cancer process are discussed and previous and novel HSP90-based therapeutic strategies in cancer treatment are summarized. Furthermore, prospective HSP90-targeting candidates are proposed for their future evaluation as cancer treatments. Contents 1. Introduction 2. Structure and biological function of HSP90 3. HSP90 as a druggable target in cancer therapy 4. Old and new anti-neoplastic treatments targeting HSP90 5. Conclusions and future perspectives