ArticleOncotarget2017
The hypoxia-activated prodrug evofosfamide in combination with multiple regimens of radiotherapy.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy.Frontiers in oncology · 2021Pooled it
- Evofosfamide for the treatment of human papillomavirus-negative head and neck squamous cell carcinoma.JCI insight · 2018Trial
- Compound Library Screening Identified Cladribine as a Novel Radiosensitizer for Prostate Cancer.Cancer science · 2026Article
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- Targeting Tumor-Associated Hypoxia with Bioreductively Activatable Prodrug Conjugates Derived from Dihydronaphthalene, Benzosuberene, and Indole-based Inhibitors of Tubulin Polymerization.RSC medicinal chemistry · 2025Article
- Article
- Review
- The Role of Imaging Biomarkers to Guide Pharmacological Interventions Targeting Tumor Hypoxia.Frontiers in pharmacology · 2022Review
- Switching on prodrugs using radiotherapy.Nature chemistry · 2021Article
- Interfering with Tumor Hypoxia for Radiotherapy Optimization.Journal of experimental & clinical cancer research : CR · 2021Review
- Relevance of the combination of external beam radiotherapy with the hypoxia-activated prodrug ICF05016 in an experimental model of extraskeletal myxoid chondrosarcoma.Investigational new drugs · 2021Article
- The Hypoxia-Activated Prodrug TH-302: Exploiting Hypoxia in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Deep-learning and MR images to target hypoxic habitats with evofosfamide in preclinical models of sarcoma.Theranostics · 2021Article
- Combining hypoxia-activated prodrugs and radiotherapy in silico: Impact of treatment scheduling and the intra-tumoural oxygen landscape.PLoS computational biology · 2020Article
- In silico analysis of hypoxia activated prodrugs in combination with anti angiogenic therapy through nanocell delivery.PLoS computational biology · 2020Article
- Review
- Evofosfamide sensitizes esophageal carcinomas to radiation without increasing normal tissue toxicity.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2019Article
- HPV, hypoxia and radiation response in head and neck cancer.The British journal of radiology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The promising treatment combination of ionizing radiation (IR) with a hypoxia-activated prodrug (HAP) is based on biological cooperation. Here we investigated the hypoxia-activated prodrug evofosfamide in combination with different treatment regimens of IR against lung A549- and head&neck UT-SCC-14-derived tumor xenografts. DNA damage-related endpoints and clonogenic cell survival of A549 and UT-SCC-14 carcinoma cells were probed under normoxia and hypoxia.Evofosfamide (TH-302) induced DNA-damage and a dose-dependent antiproliferative response in A549 cells on cellular pretreatment under hypoxia, and supra-additively reduced clonogenic survival in combination with IR. Concomitant treatment of A549-derived tumor xenografts with evofosfamide and fractionated irradiation induced the strongest treatment response in comparison to the corresponding neoadjuvant and adjuvant regimens. Adjuvant evofosfamide was more potent than concomitant and neoadjuvant evofosfamide when combined with a single high dose of IR. Hypoxic UT-SCC-14 cells and tumor xenografts thereof were resistant to evofosfamide alone and in combination with IR, most probably due to reduced P450 oxidoreductase expression, which might act as major predictive determinant of sensitivity to HAPs.In conclusion, evofosfamide with IR is a potent combined treatment modality against hypoxic tumors. However, the efficacy and the therapeutic outcome of this combined treatment modality is, as indicated here in preclinical tumor models, dependent on scheduling parameters and tumor type, which is most probably related to the status of respective HAP-activating oxidoreductases. Further biomarker development is necessary for the launch of successful clinical trials.
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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.