HSP90: A promising target for NSCLC treatments.

Yue Zhu, Zhaoxia Dai

European journal of pharmacology 2024 Mar 15

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The emergence of targeted therapies and immunotherapies has improved the overall survival of patients with nonsmall cell lung cancer (NSCLC), but the 5-year survival rate remains low. New drugs are needed to overcome this dilemma. Moreover, the significant correlation between various client proteins of heat-shock protein (HSP) 90 and tumor occurrence, progression, and drug resistance suggests that HSP90 is a potential therapeutic target for NSCLC. However, the outcomes of clinical trials for HSP90 inhibitors have been disappointing, indicating significant toxicity of these drugs and that further screening of the beneficiary population is required. NSCLC patients with oncogenic-driven gene mutations or those at advanced stages who are resistant to multi-line treatments may benefit from HSP90 inhibitors. Enhancing the therapeutic efficacy and reducing the toxicity of HSP90 inhibitors can be achieved via the optimization of their drug structure, using them in combination therapies with low-dose HSP90 inhibitors and other drugs, and via targeted administration to tumor lesions. Here, we provide a review of the recent research on the role of HSP90 in NSCLC and summarize relevant studies of HSP90 inhibitors in NSCLC. Copyright © 2024. Published by Elsevier B.V.