ArticleNature communications2018
Interplay between hypoxia and androgen controls a metabolic switch conferring resistance to androgen/AR-targeted therapy.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
What it found
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Who cites it
54 citing papers in PubMed, 73 citations in OpenAlex.
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- A Stress-Adaptive Lipid Kinase Axis Defines Metabolic Vulnerabilities in Neuroendocrine Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Copper-EGCG nanoreactor orchestrates dual-metabolic assault and self-amplified cuproptosis for immunogenic prostate cancer therapy.Journal of nanobiotechnology · 2026Article
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- Breaking the bonds: targeting protein dimerization for prostate cancer therapy.Endocrinology · 2026Review
- Insulin-like growth factor binding protein-3 serves as a biomarker for resistance to enzalutamide in prostate cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Review
- KDM5B-driven glucose metabolic reprogramming promotes enzalutamide resistance in prostate cancer via the lactate/hnRNPA1 lactylation/AR-V7 axis.Molecular cancer · 2026Article
- Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution.Genome research · 2026Article
- Androgen receptor may promote tumor progression via TTF-1/EGFR pathway in metastatic nasopharyngeal carcinoma.Translational oncology · 2026Article
- Theranostic Nanoparticles in Prostate Cancer: Disrupting Hypoxia-Induced Glycolysis by Targeting Hypoxia-Inducible Factor-1 Alpha and Downstream Metabolites.Cancer medicine · 2026Review
- LHX2 Rewires the Metabolic and Epigenetic Landscape to Drive Tumor Progression in Prostate Cancer.Cancer research · 2025Article
- MRI of ASCT2-mediated amino acid uptake in xenograft tumor models.Research square · 2025Article
- Comprehensive investigation of the molecular basis of cancer dependencies suggests therapeutic options for breast cancer.Cancer biology & medicine · 2025Article
- Article
- Understanding Enzalutamide-Resistance Based on a Functional Single-Cell Approach.The Prostate · 2025Article
- Small-molecule RNA therapeutics to target prostate cancer.Cancer cell · 2025Article
- Heterogeneous Responses to High-Dose Testosterone in Castration-Resistant Prostate Cancer Tumors with Mixed Rb-Proficient and Rb-Deficient Cells.Molecular cancer therapeutics · 2025Article
- Prostate cancer exploits BRD9-driven metabolic reprogramming to shape the aggressive phenotype.Cell death & disease · 2025Article
- 5-Aminolevulinic Acid: A Novel Approach to Improving Radioresistance in Prostate Cancer.Cancers · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Despite recent advances, the efficacy of androgen/androgen receptor (AR)-targeted therapy remains limited for many patients with metastatic prostate cancer. This is in part because prostate cancers adaptively switch to the androgen/AR-independent pathway for survival and growth, thereby conferring therapy resistance. Tumor hypoxia is considered as a major cause of treatment resistance. However, the exact mechanism is largely unclear. Here we report that chronic-androgen deprivation therapy (ADT) in the condition of hypoxia induces adaptive androgen/AR-independence, and therefore confers resistance to androgen/AR-targeted therapy, e.g., enzalutamide. Mechanistically, this is mediated by glucose-6-phosphate isomerase (GPI), which is transcriptionally repressed by AR in hypoxia, but restored and increased by AR inhibition. In turn, GPI maintains glucose metabolism and energy homeostasis in hypoxia by redirecting the glucose flux from androgen/AR-dependent pentose phosphate pathway (PPP) to hypoxia-induced glycolysis pathway, thereby reducing the growth inhibitory effect of enzalutamide. Inhibiting GPI overcomes the therapy resistance in hypoxia in vitro and increases enzalutamide efficacy in vivo.
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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.