ArticleCells2019
Impact of Tumour Hypoxia on Evofosfamide Sensitivity in Head and Neck Squamous Cell Carcinoma Patient-Derived Xenograft Models.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- Bimodality imaging as a companion to evaluate antitumour efficacy of TH-302 in experimental chondrosarcoma.EJNMMI research · 2025Article
- Barcoded Orthotopic Patient-Derived Head & Neck Squamous Cell Carcinoma Model Demonstrating Clonal Stability and Maintenance of Cancer Driver Mutational Landscape.Cancer medicine · 2025Article
- Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models.Molecular oncology · 2024Article
- Mitochondria-targeting multifunctional nanoplatform for cascade phototherapy and hypoxia-activated chemotherapy.Journal of nanobiotechnology · 2022Article
- Genomic and Molecular Signatures of Successful Patient-Derived Xenografts for Oral Cavity Squamous Cell Carcinoma.Frontiers in oncology · 2022Article
- The relevance between hypoxia-dependent spatial transcriptomics and the prognosis and efficacy of immunotherapy in claudin-low breast cancer.Frontiers in immunology · 2022Article
- Phase IB study of sorafenib and evofosfamide in patients with advanced hepatocellular and renal cell carcinomas (NCCTG N1135, Alliance).Investigational new drugs · 2021Article
- Chitosan oligosaccharide decorated liposomes combined with TH302 for photodynamic therapy in triple negative breast cancer.Journal of nanobiotechnology · 2021Article
- Hypoxia and its therapeutic possibilities in paediatric cancers.British journal of cancer · 2021Review
- 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
- Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumour hypoxia is a marker of poor prognosis and failure of chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC), providing a strategy for therapeutic intervention in this setting. To evaluate the utility of the hypoxia-activated prodrug evofosfamide (TH-302) in HNSCC, we established ten early passage patient-derived xenograft (PDX) models of HNSCC that were characterised by their histopathology, hypoxia status, gene expression, and sensitivity to evofosfamide. All PDX models closely resembled the histology of the patient tumours they were derived from. Pimonidazole-positive tumour hypoxic fractions ranged from 1.7-7.9% in line with reported HNSCC clinical values, while mRNA expression of the Toustrup hypoxia gene signature showed close correlations between PDX and matched patient tumours, together suggesting the PDX models may accurately model clinical tumour hypoxia. Evofosfamide as a single agent (50 mg/kg IP, qd × 5 for three weeks) demonstrated antitumour efficacy that was variable across the PDX models, ranging from complete regressions in one p16-positive PDX model to lack of significant activity in the three most resistant models. Despite all PDX models showing evidence of tumour hypoxia, and hypoxia being essential for activation of evofosfamide, the antitumour activity of evofosfamide only weakly correlated with tumour hypoxia status determined by pimonidazole immunohistochemistry. Other candidate evofosfamide sensitivity genes-
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