ArticleOncotarget2017
Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Ascorbate-driven quinone redox cycling as a pro-oxidant anticancer strategy.Redox biology · 2026Review
- Insight into the structural and dynamic properties of novel HSP90 inhibitors through DFT calculations and molecular dynamics simulations.Journal of molecular modeling · 2024Article
- Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance.International journal of molecular sciences · 2023Article
- Smart Nanofiber Mesh with Locally Sustained Drug Release Enabled Synergistic Combination Therapy for Glioblastoma.Nanomaterials (Basel, Switzerland) · 2023Article
- The hypoxia-inducible factor-1α in stemness and resistance to chemotherapy in gastric cancer: Future directions for therapeutic targeting.Frontiers in cell and developmental biology · 2023Review
- Effects of Radiotherapy in Combination With Irinotecan and 17-AAG on Bcl-2 and Caspase 3 Gene Expression in Colorectal Cancer Cells.Journal of lasers in medical sciences · 2022Article
- Cell Cycle, Telomeres, and Telomerase inCells · 2021Review
- Functional genomic analysis identifies drug targetable pathways in invasive and metastatic cutaneous squamous cell carcinoma.Cold Spring Harbor molecular case studies · 2020Article
- Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation.International journal of molecular sciences · 2019Article
- Heat shock protein 90α couples with the MAPK-signaling pathway to determine meiotic maturation of porcine oocytes.Journal of animal science · 2018Article
- Sensitization of multidrug-resistant cancer cells to Hsp90 inhibitors by NSAIDs-induced apoptotic and autophagic cell death.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
17 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice. We also evaluated the expression of HSP90 by immunohistochemistry in human GBC tumors.In vitro assays showed that 17-AAG and GA significantly reduced the expression of HSP90 target proteins, including EGFR, AKT, phospho-AKT, Cyclin B1, phospho-ERK and Cyclin D1. These molecular changes were consistent with reduced cell viability and cell migration and promotion of G2/M cell cycle arrest and apoptosis observed in our in vitro studies.In vivo, 17-AAG showed efficacy in reducing subcutaneous tumors size, exhibiting a 69.6% reduction in tumor size in the treatment group compared to control mice (p < 0.05).The HSP90 immunohistochemical staining was seen in 182/209 cases of GBC (87%) and it was strongly expressed in 70 cases (33%), moderately in 58 cases (28%), and weakly in 54 cases (26%).Our pre-clinical observations strongly suggest that the inhibition of HSP90 function by HSP90 inhibitors is a promising therapeutic strategy for gallbladder cancer that may benefit from new HSP90 inhibitors currently in development.
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