ArticleNature metabolism2019
Characterization of Hypoxia-associated Molecular Features to Aid Hypoxia-Targeted Therapy.
Article in Nature metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 1 of them a synthesis that pooled it.
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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
145 citing papers in PubMed, 1 synthesis or guideline pooled it, 258 citations in OpenAlex.
- The combined signatures of hypoxia and cellular landscape provides a prognostic and therapeutic biomarker in hepatitis B virus-related hepatocellular carcinoma.International journal of cancer · 2022Pooled it
- Chemical vs Physical Radioenhancement from TiONano letters · 2025Trial
- Magnetic nanorobots in oncology: From targeted drug delivery to smart theranostic systems.Materials today. Bio · 2026Review
- Iron-based magnetic nanoplatforms for immune microenvironment remodeling and cancer immunotherapy: progress and prospects.Journal of nanobiotechnology · 2026Review
- Spheroids reveal hypoxia‑driven spatial restriction of adenoviral infection.Scientific reports · 2026Article
- Current Studies on the Hypoxic Tumor Microenvironment in Thyroid Cancer: From Molecular Mechanisms to Clinical Therapeutic Perspectives.Biomedicines · 2026Review
- Overcoming tumour resistance in cancer immunotherapy through predictive and pharmacodynamic biomarkers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Hypoxia-responsive CEA-targeted CAR T cells in CEA-positive solid tumors through intraperitoneal or intravenous infusion: a phase 1 trial.Nature cancer · 2026Article
- VPS34 in Autophagy, Cancer, and Cancer Therapy.Cells · 2026Review
- Intrinsic Tumor Aggressiveness Dictates Hypoxia-Driven Metabolic Programs in Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- Demography-dependent variability in the human tumor mycobiome.Microbiology spectrum · 2026Article
- Role of hypoxia-inducible factor - 1 alpha on the progression of cervical intraepithelial neoplasia and cervical cancer: a narrative review.Frontiers in oncology · 2026Review
- Hypoxic microenvironment in cancer: role in metabolic reprogramming.Frontiers in oncology · 2026Review
- eIF3d and eIF3e mediate selective translational control of hypoxia that can be inhibited by small molecules.Cell reports · 2025Article
- Identification of the important role of CA9 in immune infiltration and prognosis in cervical cancer.Future science OA · 2025Article
- Hypoxia-Induced Extracellular Vesicles and Non-Coding RNAs in Cancer: A Systematic Review of Tumor Dynamics and Therapeutic Implications in Preclinical Animal Models.Biomedicines · 2025Review
- Mitochondrial DNA-Mediated Intercellular Communication via Extracellular Vesicles Under Hypoxic Stress to Drive HCC Progression.Cancer science · 2025Article
- Targeting ribosomes reprograms the tumour microenvironment and augments cancer immunotherapy.British journal of cancer · 2025Article
- ACTL6A regulates the Warburg effect through coordinated activation of AP-1 signaling in head and neck squamous cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Targeting Tumor-Associated Hypoxia with Bioreductively Activatable Prodrug Conjugates Derived from Dihydronaphthalene, Benzosuberene, and Indole-based Inhibitors of Tubulin Polymerization.RSC medicinal chemistry · 2025Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 2 countries.
Funding
Abstract
Tumor hypoxia is a major contributor to resistance to anti-cancer therapies. Given that the results of hypoxia-targeted therapy trials have been disappointing, a more personalized approach may be needed. Here we characterize multi-OMIC molecular features associated with tumor hypoxia and identify molecular alterations that correlate with both drug-resistant and drug-sensitive responses to anti-cancer drugs. Based on a well-established hypoxia gene expression signature, we classify about 10,000 tumor samples into hypoxia score-high and score-low groups across different cancer types from The Cancer Genome Atlas and demonstrate their prognostic associations. We then identify various types of molecular features associated with hypoxia status that correlate with drug resistance but, in some cases, also with drug sensitivity, contrasting the conventional view that hypoxia confers drug resistance. We further show that 110 out of 121 (90.9%) clinically actionable genes can be affected by hypoxia status and experimentally validate the predicted effects of hypoxia on the response to several drugs in cultured cells. Our study provides a comprehensive molecular-level understanding of tumor hypoxia and may have practical implications for clinical cancer therapy.
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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.