ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non-Small Cell Lung Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 86 citations in OpenAlex.
- Neoadjuvant camrelizumab combined with metronomic chemotherapy in patients with advanced esophageal squamous cell carcinoma: a pilot randomized phase 2 trial.BMC medicine · 2026Trial
- Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study.Acta oncologica (Stockholm, Sweden) · 2025Trial
- Tumour hypoxia in clinical oncology: imaging, therapeutic strategies, and translational challenges.Clinical and translational radiation oncology · 2027Review
- Malaria and cancer: common features and interactions.Trends in parasitology · 2026Review
- Drug repurposing in KRAS G12C-mutant NSCLC: a focus on resistance mechanisms and clinical strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Redox and structural determinants of mitochondrial complex III inhibition by triphenylphosphonium-conjugated atovaquone analogs.Redox biology · 2026Article
- New Functions of Mitochondrial Dysfunction in Gastric Cancer: From Molecular Processes to Potential Treatments.International journal of molecular sciences · 2026Review
- Structure-guided optimisation of fenofibrate-derived oxidative phosphorylation inhibitors to modify tumour hypoxia.RSC medicinal chemistry · 2026Article
- The oxidative phosphorylation inhibitor, atovaquone, upregulates PD-L1 via activation of the ATM/ATR DNA damage response pathway.Research square · 2026Article
- Identifying Key Pathogenic Mechanisms in Recurrent Glioblastoma Through Bioinformatics Analysis.Current medicinal chemistry · 2026Article
- Radiation-induced network rewiring in cancer: systems-level insights into environmental radioactivity and precision oncology.Frontiers in bioinformatics · 2026Review
- Emerging Nanoplatforms are Effective Against Tumor Hypoxia.International journal of nanomedicine · 2026Review
- Development of Selective and Soluble Mitochondrial Complex 1 Inhibitors Derived from Papaverine for Radiosensitization of Cancer.Journal of medicinal chemistry · 2025Article
- A guide to reactive oxygen species in tumour hypoxia: measurement and therapeutic implications.Molecular oncology · 2025Review
- Itaconate suppresses neonatal intestinal inflammation via metabolic reprogramming of M1 macrophage.Clinical and translational medicine · 2025Article
- A micro-metabolic rewiring assay for assessing hypoxia-associated cancer metabolic heterogeneity.Bioactive materials · 2025Article
- Image-guided targeting of mitochondrial metabolism sensitizes pediatric malignant rhabdoid tumors to low-dose radiotherapy.Science advances · 2025Article
- Atovaquone-induced activation of the PERK/eIF2α signaling axis mitigates metabolic radiosensitisation.Cell communication and signaling : CCS · 2025Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- Hypoxia studies in non‑small cell lung cancer: Pathogenesis and clinical implications (Review).Oncology reports · 2025Review
Corrections and comments
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Authors and funding
32 authors at 7 institutions in 2 countries.
Funding
Abstract
purposeTumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial to determine whether the antimalarial drug atovaquone, a known mitochondrial inhibitor, reduces hypoxia in non-small cell lung cancer (NSCLC). PATIENTS AND
methodsPatients with NSCLC scheduled for surgery were recruited sequentially into two cohorts: cohort 1 received oral atovaquone at the standard clinical dose of 750 mg twice daily, while cohort 2 did not. Primary imaging endpoint was change in tumor hypoxic volume (HV) measured by hypoxia PET-CT. Intercohort comparison of hypoxia gene expression signatures using RNA sequencing from resected tumors was performed.
resultsThirty patients were evaluable for hypoxia PET-CT analysis, 15 per cohort. Median treatment duration was 12 days. Eleven (73.3%) atovaquone-treated patients had meaningful HV reduction, with median change -28% [95% confidence interval (CI), -58.2 to -4.4]. In contrast, median change in untreated patients was +15.5% (95% CI, -6.5 to 35.5). Linear regression estimated the expected mean HV was 55% (95% CI, 24%-74%) lower in cohort 1 compared with cohort 2 (
conclusionsThis is the first clinical evidence that targeting tumor mitochondrial metabolism can reduce hypoxia and produce relevant antitumor effects at the mRNA level. Repurposing atovaquone for this purpose may improve treatment outcomes for NSCLC.
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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.