ArticleOncotarget2018
Dual targeting of HSP70 does not induce the heat shock response and synergistically reduces cell viability in muscle invasive bladder cancer.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Hsp70: A Multifunctional Chaperone in Maintaining Proteostasis and Its Implications in Human Disease.Cells · 2025Review
- Review
- Article
- Synthetic Small Molecule Modulators of Hsp70 and Hsp40 Chaperones as Promising Anticancer Agents.International journal of molecular sciences · 2023Review
- Heat Shock Transcription Factor 2 Is Significantly Involved in Neurodegenerative Diseases, Inflammatory Bowel Disease, Cancer, Male Infertility, and Fetal Alcohol Spectrum Disorder: The Novel Mechanisms of Several Severe Diseases.International journal of molecular sciences · 2022Review
- The heat shock response and small molecule regulators.European journal of medicinal chemistry · 2021Review
- The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.Archives of toxicology · 2021Review
- Hsp70 acts as a fine-switch that controls E3 ligase CHIP-mediated TAp63 and ΔNp63 ubiquitination and degradation.Nucleic acids research · 2021Article
- HSF1: Primary Factor in Molecular Chaperone Expression and a Major Contributor to Cancer Morbidity.Cells · 2020Review
- Hsp70 and the Unfolded Protein Response as a Challenging Drug Target and an Inspiration for Probe Molecule Development.ACS medicinal chemistry letters · 2020Article
- Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors.International journal of molecular sciences · 2019Review
- Heat Shock Proteins and Ovarian Cancer: Important Roles and Therapeutic Opportunities.Cancers · 2019Review
- Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond.International journal of molecular sciences · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Muscle invasive bladder cancer (MIBC) is a common malignancy and major cause of morbidity worldwide. Over the last decade mortality rates for MIBC have not decreased as compared to other cancers indicating a need for novel strategies. The molecular chaperones HSP70 and HSP90 fold and maintain the 3-dimensional structures of numerous client proteins that signal for cancer cell growth and survival. Inhibition of HSP70 or HSP90 results in client protein degradation and associated oncogenic signaling. Here we targeted HSP70 and HSP90 with small molecule inhibitors that trap or block each chaperone in a low client-affinity "open" conformation. HSP70 inhibitors, VER155008 (VER) and MAL3-101 (MAL), along with HSP90 inhibitor, STA-9090 (STA), were tested alone and in combination for their ability to reduce cell viability and alter protein levels in 4 MIBC cell lines. When combined, VER+MAL synergistically reduced cell viability in each MIBC cell line while not inducing expression of heat shock proteins (HSPs). STA+MAL also synergistically reduced cell viability in each cell line but induced expression of cytoprotective HSPs indicating the merits of targeting HSP70 with VER+MAL. Additionally, we observed that STA induced the expression of the stress-related transcription factor HSF2 while reducing levels of the co-chaperone TTI1.
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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.