ArticleCell death and differentiation2020
Selecting the first chemical molecule inhibitor of HSP110 for colorectal cancer therapy.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Prognostic role of HSPs in human colorectal cancer: a systematic review and meta-analysis.BMC cancer · 2026Pooled it
- Combining PD-L1 blockade with a second-generation HSP110 inhibitor enhances antitumor immunity in colorectal cancer.Cell death & disease · 2026Article
- Heat Shock Proteins as Targets for Cancer Therapeutics.Journal of clinical medicine · 2026Review
- ATP modulates holdase activity of fungal and human 110-kilodalton heat shock proteins to promote protein folding.Protein science : a publication of the Protein Society · 2026Article
- Article
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Targeting chaperone modifications: Innovative approaches to cancer treatment.The Journal of biological chemistry · 2024Review
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- First-in-class inhibitor of HSP110 blocks BCR activation through SYK phosphorylation in diffuse large B-cell lymphoma.Leukemia · 2024Article
- A first-in-class inhibitor of HSP110 to potentiate XPO1-targeted therapy in primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Review
- HSPA4 Expression is Correlated with Melanoma Cell Proliferation, Prognosis, and Immune Regulation.Clinical, cosmetic and investigational dermatology · 2024Article
- Inhibition of Hsp110-STAT3 interaction in endothelial cells alleviates vascular remodeling in hypoxic pulmonary arterial Hypertension model.Respiratory research · 2023Article
- A first-in-class inhibitor of Hsp110 molecular chaperones of pathogenic fungi.Nature communications · 2023Article
- Heat Shock Proteins in Tooth Development and Injury Repair.International journal of molecular sciences · 2023Review
- Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches.Cancers · 2023Review
- HSP105 suppresses the progression of cutaneous squamous cell carcinoma by activating the P53 signaling pathway.American journal of cancer research · 2023Article
- Extracellular HSPs: The Potential Target for Human Disease Therapy.Molecules (Basel, Switzerland) · 2022Review
- Review
- Dual roles of HSP70 chaperone HSPA1 in quality control of nascent and newly synthesized proteins.The EMBO journal · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pro-survival stress-inducible chaperone HSP110 is the only HSP for which a mutation has been found in a cancer. Multicenter clinical studies demonstrated a direct association between HSP110 inactivating mutation presence and excellent prognosis in colorectal cancer patients. Here, we have combined crystallographic studies on human HSP110 and in silico modeling to identify HSP110 inhibitors that could be used in colorectal cancer therapy. Two molecules (foldamers 33 and 52), binding to the same cleft of HSP110 nucleotide-binding domain, were selected from a chemical library (by co-immunoprecipitation, AlphaScreening, Interference-Biolayer, Duo-link). These molecules block HSP110 chaperone anti-aggregation activity and HSP110 association to its client protein STAT3, thereby inhibiting STAT3 phosphorylation and colorectal cancer cell growth. These effects were strongly decreased in HSP110 knockdown cells. Foldamer's 33 ability to inhibit tumor growth was confirmed in two colorectal cancer animal models. Although tumor cell death (apoptosis) was noted after treatment of the animals with foldamer 33, no apparent toxicity was observed, notably in epithelial cells from intestinal crypts. Taken together, we identified the first HSP110 inhibitor, a possible drug-candidate for colorectal cancer patients whose unfavorable outcome is associated to HSP110.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.