ReviewCells2021
HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells.
Review in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- Progress, critical challenges, and translational prospects of intranasal administration of botanical essential oils for the treatment of depression.Frontiers in pharmacology · 2025Pooled it
- Molecular Pathways Linking High-Fat Diet and PMBiomolecules · 2024Pooled it
- Review
- Clinically approved HIF-PHIs modulate redox metabolism, cell growth, and angiogenesis independent of HIF-1α/HIF-2α.Redox biology · 2026Article
- Pharmacological Targeting of Angiogenesis in Head and Neck Cancer: Molecular Mechanisms and Emerging Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Unveiling the novel role of PGAM5 in rewiring metabolism through PI3K/AKT/mTOR signaling in acute myelogenous leukemia.Scientific reports · 2026Article
- PTBP1 is upregulated in response to Zika virus infection and restrains viral replication by hijacking viral NS1 protein to induce NS1 degradation.Journal of virology · 2026Article
- LDHA protects vascular endothelial cells from oxidative stress‑induced mitochondrial damage via HIF‑1α activation and glycolytic reprogramming.Molecular medicine reports · 2026Article
- Nuclear hexokinase 2 couples hyperglycemia to MYC-driven glycolytic and stemness programs in bladder cancer.Cell death & disease · 2026Article
- Beyond the neuron: Exosomes as intercellular modulators of mitochondrial networks in the pathogenesis and treatment of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Hypoxia and HIF signalling in tumour microenvironment: linking immune evasion, metabolic rewiring and epigenetic regulation.Expert reviews in molecular medicine · 2026Review
- Exploring the role of metabolic disorders and gut microbiome in immune checkpoint regulation in cancer: PI3K/AKT/mTOR focus.Journal of physiology and biochemistry · 2026Review
- Vitexin Attenuates the Growth and Glycolysis of Acute Myeloid Leukemia Cells by Suppressing the HIF-1α-Modulated YAP Pathway Under Hypoxic Conditions.The Kaohsiung journal of medical sciences · 2026Article
- A novel molecule ZYZ329 targeting histone methyltransferase SMYD3 suppresses pathological angiogenesis via the driven mitochondrial ROS/HIF-1α/VEGFA axis.Journal of translational medicine · 2026Article
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Self-supervised pretraining with NuSPIRe unlocks nuclear morphology-driven insights in spatial omics.Genome biology · 2026Article
- Differential roles of the type I and II secretion systems for the intracellular ABC141 Acinetobacter baumannii infection, which elicits an atypical hypoxia response in endothelial cells.PLoS pathogens · 2026Article
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In solid tumours, cancer cells exist within hypoxic microenvironments, and their metabolic adaptation to this hypoxia is driven by HIF-1 transcription factor, which is overexpressed in a broad range of human cancers. HIF inhibitors are under pre-clinical investigation and clinical trials, but there is evidence that hypoxic cancer cells can adapt metabolically to HIF-1 inhibition, which would provide a potential route for drug resistance. Here, we review accumulating evidence of such adaptions in carbohydrate and creatine metabolism and other HIF-1-independent mechanisms that might allow cancers to survive hypoxia despite anti-HIF-1 therapy. These include pathways in glucose, glutamine, and lipid metabolism; epigenetic mechanisms; post-translational protein modifications; spatial reorganization of enzymes; signalling pathways such as Myc, PI3K-Akt, 2-hyxdroxyglutarate and AMP-activated protein kinase (AMPK); and activation of the HIF-2 pathway. All of these should be investigated in future work on hypoxia bypass mechanisms in anti-HIF-1 cancer therapy. In principle, agents targeted toward HIF-1β rather than HIF-1α might be advantageous, as both HIF-1 and HIF-2 require HIF-1β for activation. However, HIF-1β is also the aryl hydrocarbon nuclear transporter (ARNT), which has functions in many tissues, so off-target effects should be expected. In general, cancer therapy by HIF inhibition will need careful attention to potential resistance mechanisms.
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What OpenQuestion holds
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.