ArticleProceedings of the National Academy of Sciences of the United States of America2018
Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 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 96 papers.
What it found
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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.
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Who cites it
96 citing papers in PubMed.
- Structure-guided optimisation of fenofibrate-derived oxidative phosphorylation inhibitors to modify tumour hypoxia.RSC medicinal chemistry · 2026Article
- Identification of non-oncology drugs with activity against inflammatory and triple-negative breast cancer cell lines.Oncology letters · 2026Article
- Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review).Molecular and clinical oncology · 2026Review
- A Modular Chemoenzymatic Cascade Simplifies Divergent Synthesis of Natural and Unnatural Benzylisoquinoline Alkaloids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondria-targeted strategies in cancer radiotherapy: from ROS regulation to immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control.International journal of pharmaceutics: X · 2025Review
- Development of Selective and Soluble Mitochondrial Complex 1 Inhibitors Derived from Papaverine for Radiosensitization of Cancer.Journal of medicinal chemistry · 2025Article
- Targeting mitochondria and programmed cell death as potential interventions for metastatic castration-resistant prostate cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Nano-orchestrated magnetotactic-like navigation for electromagnetic theranostics and immune enhancement via photoautotrophic oxygenation, mild hyperthermia, and ferroptosis.Journal of nanobiotechnology · 2025Article
- Atovaquone-induced activation of the PERK/eIF2α signaling axis mitigates metabolic radiosensitisation.Cell communication and signaling : CCS · 2025Article
- Papaverine Targets STAT Signaling: A Dual-Action Therapy Option Against SARS-CoV-2.Journal of medical virology · 2025Article
- Hypoxia studies in non‑small cell lung cancer: Pathogenesis and clinical implications (Review).Oncology reports · 2025Review
- Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation.The EMBO journal · 2025Article
- Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: AInternational journal of molecular sciences · 2025Article
- The interplay between the tumor microenvironment and tumor-derived small extracellular vesicles in cancer development and therapeutic response.Cancer biology & therapy · 2024Review
- Investigating impacts of the mycothiazole chemotype as a chemical probe for the study of mitochondrial function and aging.GeroScience · 2024Article
- Mitochondria in tumor immune surveillance and tumor therapies targeting mitochondria.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Targeting Radiation Resistance in Oesophageal Adenocarcinoma with Pyrazinib-Functionalised Gold Nanoparticles.Cancers · 2024Article
- Realtime and noninvasive assessment of endotracheal tube displacement using near-infrared and visible cameras.Biomedical optics express · 2024Article
- The Interplay between Autophagy and Mitochondria in Cancer.International journal of molecular sciences · 2024Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
Tumor hypoxia reduces the effectiveness of radiation therapy by limiting the biologically effective dose. An acute increase in tumor oxygenation before radiation treatment should therefore significantly improve the tumor cell kill after radiation. Efforts to increase oxygen delivery to the tumor have not shown positive clinical results. Here we show that targeting mitochondrial respiration results in a significant reduction of the tumor cells' demand for oxygen, leading to increased tumor oxygenation and radiation response. We identified an activity of the FDA-approved drug papaverine as an inhibitor of mitochondrial complex I. We also provide genetic evidence that papaverine's complex I inhibition is directly responsible for increased oxygenation and enhanced radiation response. Furthermore, we describe derivatives of papaverine that have the potential to become clinical radiosensitizers with potentially fewer side effects. Importantly, this radiosensitizing strategy will not sensitize well-oxygenated normal tissue, thereby increasing the therapeutic index of radiotherapy.
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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.