ArticleScience translational medicine2021
Avasopasem manganese synergizes with hypofractionated radiation to ablate tumors through the generation of hydrogen peroxide.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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.
An Adaptive Phase I/II Dose Escalation Trial of Stereotactic Body Radiation Therapy in Combination With Radiomodulating Agent GC4419 in Locally Advanced Pancreatic Adenocarcinoma
ROMAN: Reduction in Oral Mucositis With Avasopasem Manganese (GC4419) - Phase 3 Trial in Patients Receiving Chemoradiotherapy for Locally-Advanced, Non-Metastatic Head and Neck Cancer
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors.Cancer immunology, immunotherapy : CII · 2023Pooled it
- Stereotactic body radiotherapy with or without selective dismutase mimetic in pancreatic adenocarcinoma: an adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial.The Lancet. Oncology · 2023Trial
- Precise and rapid release of X-ray activated autophagy inhibitors for radiotherapy sensitization of hypopharyngeal carcinoma.Materials today. Bio · 2026Article
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- Superoxide Mediates Radiation-Induced Cardiac Injury and Activates the Canonical Transforming Growth Factor-Beta Signaling Pathway.Journal of the American Heart Association · 2026Article
- Avasopasem manganese acts as both a radioprotector and a radiomitigator of radiation-induced acute or late effects.Frontiers in oncology · 2026Article
- Avasopasem manganese treatment for severe oral mucositis from chemoradiotherapy for locally advanced head and neck cancer: phase 3 randomized controlled trial (ROMAN).EClinicalMedicine · 2025Article
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Benefit of Avasopasem Manganese on Severe Oral Mucositis in Head and Neck Cancer in the ROMAN Trial: Unplanned Secondary Analysis.Advances in radiation oncology · 2025Article
- Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy.Journal for immunotherapy of cancer · 2024Review
- Crystal OH mediating pathway for hydrogen peroxide production via two-electron water oxidation in non-carbonate electrolytes.Nature communications · 2024Article
- Cancer treatment-related xerostomia: basics, therapeutics, and future perspectives.European journal of medical research · 2024Review
- Targeting catalase in cancer.Redox biology · 2024Review
- Balanced Duality: HInternational journal of molecular sciences · 2024Review
- Targeting ROS in cancer: rationale and strategies.Nature reviews. Drug discovery · 2024Review
- Trace elements in pancreatic cancer.Cancer medicine · 2024Review
- Programmable melanoma-targeted radio-immunotherapy via fusogenic liposomes functionalized with multivariate-gated aptamer assemblies.Nature communications · 2024Article
- Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing.Antioxidants (Basel, Switzerland) · 2024Article
- Stereotactic body radiotherapy plus rucosopasem in locally advanced or borderline resectable pancreatic cancer: GRECO-2 phase II study design.Future oncology (London, England) · 2024Article
- ROS production by mitochondria: function or dysfunction?Oncogene · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Avasopasem manganese (AVA or GC4419), a selective superoxide dismutase mimetic, is in a phase 3 clinical trial (NCT03689712) as a mitigator of radiation-induced mucositis in head and neck cancer based on its superoxide scavenging activity. We tested whether AVA synergized with radiation via the generation of hydrogen peroxide, the product of superoxide dismutation, to target tumor cells in preclinical xenograft models of non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, and pancreatic ductal adenocarcinoma. Treatment synergy with AVA and high dose per fraction radiation occurred when mice were given AVA once before tumor irradiation and further increased when AVA was given before and for 4 days after radiation, supporting a role for oxidative metabolism. This synergy was abrogated by conditional overexpression of catalase in the tumors. In addition, in vitro NSCLC and mammary adenocarcinoma models showed that AVA increased intracellular hydrogen peroxide concentrations and buthionine sulfoximine- and auranofin-induced inhibition of glutathione- and thioredoxin-dependent hydrogen peroxide metabolism selectively enhanced AVA-induced killing of cancer cells compared to normal cells. Gene expression in irradiated tumors treated with AVA suggested that increased inflammatory, TNFα, and apoptosis signaling also contributed to treatment synergy. These results support the hypothesis that AVA, although reducing radiotherapy damage to normal tissues, acts synergistically only with high dose per fraction radiation regimens analogous to stereotactic ablative body radiotherapy against tumors by a hydrogen peroxide-dependent mechanism. This tumoricidal synergy is now being tested in a phase I-II clinical trial in humans (NCT03340974).
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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.