ArticleProceedings of the National Academy of Sciences of the United States of America2014
HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- The rs9340799 polymorphism of the estrogen receptor alpha (ESR1) gene and its association with breast cancer susceptibility.Scientific reports · 2021Pooled it
- Plasma Heat Shock Protein 90alpha as a Biomarker for the Diagnosis of Liver Cancer: An Official, Large-scale, and Multicenter Clinical Trial.EBioMedicine · 2017Trial
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Heat shock transcription factors in development and disease.Disease models & mechanisms · 2026Review
- Dominant-negative TP53 mutations potentiated by the HSF1-regulated proteostasis network.Molecular cell · 2026Article
- HER2-Driven Breast Cancer: Role of the Chaperonin HSP90 in Modulating Response to Trastuzumab-Based Therapeutic Combinations.International journal of molecular sciences · 2025Article
- Bayesian identification of differentially expressed isoforms using a novel joint model of RNA-seq data.PLoS computational biology · 2025Article
- Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs.eLife · 2024Article
- Selection for robust metabolism in domesticated yeasts is driven by adaptation to Hsp90 stress.Science (New York, N.Y.) · 2024Article
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs.bioRxiv : the preprint server for biology · 2024Article
- Potential Value of HSP90α in Prognosis of Triple-Negative Breast Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2024Article
- Investigating the role of HSP90 in cancer cell phenotypic plasticity.Journal of breast cancer research · 2024Article
- Targeting Breast Cancer: The Familiar, the Emerging, and the Uncharted Territories.Biomolecules · 2023Review
- Exploration of anti-leukemic effect of soft coral-derived 13-acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II.The Kaohsiung journal of medical sciences · 2023Article
- Article
- Circadian disruption enhances HSF1 signaling and tumorigenesis inScience advances · 2022Article
- Review
- GroEL/S Overexpression Helps to Purge Deleterious Mutations and Reduce Genetic Diversity during Adaptive Protein Evolution.Molecular biology and evolution · 2022Article
- An allosteric inhibitor of bacterial Hsp70 chaperone potentiates antibiotics and mitigates resistance.Cell chemical biology · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
The efficacy of hormonal therapies for advanced estrogen receptor-positive breast cancers is limited by the nearly inevitable development of acquired resistance. Efforts to block the emergence of resistance have met with limited success, largely because the mechanisms underlying it are so varied and complex. Here, we investigate a new strategy aimed at the very processes by which cancers evolve resistance. From yeast to vertebrates, heat shock protein 90 (HSP90) plays a unique role among molecular chaperones by promoting the evolution of heritable new traits. It does so by regulating the folding of a diverse portfolio of metastable client proteins, many of which mediate adaptive responses that allow organisms to adapt and thrive in the face of diverse challenges, including those posed by drugs. Guided by our previous work in pathogenic fungi, in which very modest HSP90 inhibition impairs resistance to mechanistically diverse antifungals, we examined the effect of similarly modest HSP90 inhibition on the emergence of resistance to antiestrogens in breast cancer models. Even though this degree of inhibition fell below the threshold for proteotoxic activation of the heat-shock response and had no overt anticancer activity on its own, it dramatically impaired the emergence of resistance to hormone antagonists both in cell culture and in mice. Our findings strongly support the clinical testing of combined hormone antagonist-low-level HSP90 inhibitor regimens in the treatment of metastatic estrogen receptor-positive breast cancer. At a broader level, they also provide promising proof of principle for a generalizable strategy to combat the pervasive problem of rapidly emerging resistance to molecularly targeted therapeutics.
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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.