Abstract
Background and objectives: Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an essential role in tumor growth. Numerous Hsp90 inhibitors have been discovered and tested in preclinical and clinical trials. Recently, several preclinical studies have demonstrated that Hsp90 inhibitors could modulate pain sensitization. However, no studies have evaluated the impact of Hsp90 inhibitors on pain in the patients. This study aims to summarize the pain events reported in clinical trials assessing Hsp90 inhibitors and to determine the effect of Hsp90 inhibitors on pain in patients. Materials and Methods: We searched PubMed, EBSCOhost, and clinicaltrials.gov for Hsp90 inhibitor clinical trials. The pain-related adverse events were summarized. Meta-analysis was performed using the data reported in randomized controlled trials. Results: We identified 90 clinical trials that reported pain as an adverse effect, including 5 randomized controlled trials. The most common types of pain reported in all trials included headache, abdominal pain, and back pain. The meta-analysis showed that Hsp90 inhibitors increased the risk of abdominal pain significantly and appeared to increase the risk for back pain. Conclusions: In conclusion, Hsp90 inhibitor treatment could potentially increase the risk of pain. However, the meta-analysis demonstrated only moderate evidence for the connection between Hsp90 inhibitor and pain.
Highlights
Heat shock protein 90 (Hsp90) is a molecular chaperone protein found in vertebrates, invertebrates, plants, protists, and even bacteria [1]
They showed some promise in cancer treatment, the first generation of Hsp90 inhibitors, such as 17(Allylamino)-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino17-demethoxygeldanamycin (17-DMAG) have demonstrated adverse events such as hepatotoxicity, nausea, vomiting, diarrhea, and hypersensitivity [9]
This study aimed to summarize the pain-related adverse effects reported in the clinical trials testing various Hsp90 inhibitors
Summary
Heat shock protein 90 (Hsp90) is a molecular chaperone protein found in vertebrates, invertebrates, plants, protists, and even bacteria [1]. Hsp inhibitors have been tested in phase I, phase II, and phase III clinical trials, both as monotherapy and in combination with other anti-cancer agents [8]. In an effort to reduce the adverse event profile of these drugs as well as improve anti-cancer efficacy, the second generation of Hsp inhibitors has been developed. The second generation of Hsp inhibitors, including ganetespib, have shown significant improvement in the performance of cancer therapy. They may still cause neutropenia, leukopenia, anemia, pain, and diarrhea [10]. Materials and Methods: We searched PubMed, EBSCOhost, and clinicaltrials.gov for
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