Journal Article

Heat shock protein 90 (HSP90) inhibitors in gastrointestinal cancer: where do we currently stand?—A systematic review

Kim-Fuchs, Corina, Vashist, Yogesh K., Stroka, Deborah, Berger, Martin D., Banz, Vanessa M., Magyar, Christian Tibor Josef

2023

Overview

Purpose Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers. Methods We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease. Results Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors. Conclusion It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Antineoplastic Agents / Cancer Research / Clinical trials / Clinical Trials as Topic / Colorectal cancer / Colorectal carcinoma / colorectal neoplasms / Gastrointestinal cancer / gastrointestinal neoplasms / Gastrointestinal Neoplasms - drug therapy / Gastrointestinal Neoplasms - metabolism / Gastrointestinal Neoplasms - mortality / gastrointestinal system / Heat shock proteins / heat stress / heat-shock protein 90 / Hematology / HSP90 Heat-Shock Proteins - antagonists & inhibitors / HSP90 Heat-Shock Proteins - metabolism / Hsp90 protein / Humans / Inhibitor drugs / Internal Medicine / Isoxazoles - adverse effects / Isoxazoles - therapeutic use / Medicine / Medicine & Public Health / Molecular Targeted Therapy / Oncology / Resorcinols - adverse effects / Resorcinols - therapeutic use / Review / Survival / Systematic review / Toxicity / Tumors