The Effect of Heat Shock Protein 90 Inhibitor on Pain in Cancer Patients: A Systematic Review and Meta-Analysis

Miles, Victoria N.; Patel, Roma; Smith, Amanda; McCall, Ryan P.; Wu, Jun; W, Lei

doi:10.3390/medicina57010005

Cited by 4 publications

(1 citation statement)

References 27 publications

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“…Numerous non-selective Hsp90 inhibitors, including 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), have been tested in preclinical models, and clinical trials and have shown promising effects in different disease states ( Talaei et al, 2019 ). However, hepatic, cardiac, and ocular toxicities associated with Hsp90 pan inhibition have been found in clinical trials ( Talaei et al, 2019 ; Miles et al, 2020 ). Therefore, discovering Hsp90 inhibitors with fewer adverse effects would facilitate their application in human patients.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activities of novel heat shock protein 90 isoform selective inhibitors in BV-2 microglial cells

Smith,

Kliebe,

Mishra

et al. 2024

Front. Mol. Biosci.

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Heat shock protein 90 (Hsp90) is a family of chaperone proteins that consists of four isoforms: Hsp90α, Hsp90β, glucose-regulated protein 94 (Grp94), and tumor necrosis factor type 1 receptor-associated protein (TRAP1). They are involved in modulating the folding, maturation, and activation of their client proteins to regulate numerous intracellular signaling pathways. Previous studies demonstrated that pan-Hsp90 inhibitors reduce inflammatory signaling pathways resulting in a reduction of inflammation and pain but show toxicities in cancer-related clinical trials. Further, the role of Hsp90 isoforms in inflammation remains poorly understood. This study aimed to determine anti-inflammatory activities of Hsp90 isoforms selective inhibitors on the lipopolysaccharide (LPS)-induced inflammation in BV-2 cells, a murine microglial cell line. The production of inflammatory mediators such as nitric oxide (NO), interleukin 1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) was measured. We also investigated the impact of Hsp90 isoform inhibitors on the activation of nuclear factor kappa B (NF-κB), nuclear factor erythroid 2–related factor 2 (Nrf2), and mitogen-activated protein kinases (MAPKs). We found that selective inhibitors of Hsp90β reduced the LPS-induced production of NO, IL-1β, and TNF-α via diminishing the activation of NF-κB and Extracellular signal-regulated kinases (ERK) MAPK. The Hsp90α, Grp94, TRAP1 inhibitors had limited effect on the production of inflammatory mediators. These findings suggest that Hsp90β is the key player in LPS-induced neuroinflammation. Thereby providing a more selective drug target for development of medications involved in pain management that can potentially contribute to the reduction of adverse side effects associated with Hsp90 pan inhibitors.

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Section: Introductionmentioning

confidence: 99%

Anti-inflammatory activities of novel heat shock protein 90 isoform selective inhibitors in BV-2 microglial cells

Smith,

Kliebe,

Mishra

et al. 2024

Front. Mol. Biosci.

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Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis‐Related Metabolic Enzymes in the Cytoplasm

Liu,

Shen,

Zhou

et al. 2024

Advanced Science

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Heat‐shock protein 90 (Hsp90) plays a crucial role in tumorigenesis and tumor progression; however, its mechanism of action in gastric cancer (GC) remains unclear. Here, the role of Hsp90 in GC metabolism is the focus of this research. High expression of Hsp90 in GC tissues can interact with glycolysis, collectively affecting prognosis in clinical samples. Both in vitro and in vivo experiments demonstrate that Hsp90 is able to regulate the migration and stemness properties of GC cells. Metabolic phenotype analyses indicate that Hsp90 influences glycolytic metabolism. Mechanistically, Hsp90 interacts with glycolysis‐related enzymes, forming multienzyme complexes to enhance glycolysis efficiency and yield. Additionally, Hsp90 binds to cytoskeleton‐related proteins, regulating the regional distribution of glycolytic enzymes at the cell margin and lamellar pseudopods. This effect could lead to a local increase in efficient energy supply from glycolysis, further promoting epithelial‐mesenchymal transition (EMT) and metastasis. In summary, Hsp90, through its interaction with metabolic enzymes related to glycolysis, forms multi‐enzyme complexes and regulates regional distribution of glycolysis by dynamic cytoskeletal adjustments, thereby promoting the migration and stemness of GC cells. These conclusions also support the potential for a combined targeted approach involving Hsp90, glycolysis, and the cytoskeleton in clinical therapy.

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Small-molecule dual inhibitors targeting heat shock protein 90 for cancer targeted therapy

Xie

Zhang

et al. 2023

Bioorganic Chemistry

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The Effect of Heat Shock Protein 90 Inhibitor on Pain in Cancer Patients: A Systematic Review and Meta-Analysis

Cited by 4 publications

References 27 publications

Anti-inflammatory activities of novel heat shock protein 90 isoform selective inhibitors in BV-2 microglial cells

Anti-inflammatory activities of novel heat shock protein 90 isoform selective inhibitors in BV-2 microglial cells

Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis‐Related Metabolic Enzymes in the Cytoplasm

Small-molecule dual inhibitors targeting heat shock protein 90 for cancer targeted therapy

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