ArticleBritish journal of cancer2015
Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Integrative immune subtyping of HNSCC reveals clinically relevant phenotypes and treatment-associated transitions.NPJ precision oncology · 2026Article
- TH-302 (evofosfamide) monotherapy exerts anticancer activity in Ewing's sarcoma cells under hypoxia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Review
- Article
- Hypoxia-activated prodrug and antiangiogenic therapies cooperatively treat pancreatic cancer but elicit immunosuppressive G-MDSC infiltration.JCI insight · 2024Article
- Article
- Whole-tumor histogram analysis of diffusion-weighted imaging and dynamic contrast-enhanced MRI for soft tissue sarcoma: correlation with HIF-1alpha expression.European radiology · 2023Article
- Soft tissue sarcoma: correlation of dynamic contrast-enhanced magnetic resonance imaging features with HIF-1α expression and patient outcomes.Quantitative imaging in medicine and surgery · 2022Article
- Targeting HIF-1α/NOTCH1 pathway eliminates CD44Oncogene · 2022Article
- Perspectives on Hypoxia Signaling in Tumor Stroma.Cancers · 2021Review
- PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas.Oncogenesis · 2021Article
- The Hypoxia-Activated Prodrug TH-302: Exploiting Hypoxia in Cancer Therapy.Frontiers in pharmacology · 2021Review
- In silico analysis of hypoxia activated prodrugs in combination with anti angiogenic therapy through nanocell delivery.PLoS computational biology · 2020Article
- Melatonin Lowers HIF-1α Content in Human Proximal Tubular Cells (HK-2) Due to Preventing Its Deacetylation by Sirtuin 1.Frontiers in physiology · 2020Article
- Hypoxia-Targeting Drug Evofosfamide (TH-302) Enhances Sunitinib Activity in Neuroblastoma Xenograft Models.Translational oncology · 2018Article
- Efficacy of the hypoxia-activated prodrug evofosfamide (TH-302) in nasopharyngeal carcinoma in vitro and in vivo.Cancer communications (London, England) · 2018Article
- Pazopanib radio-sensitization of human sarcoma tumors.Oncotarget · 2018Article
- Challenges and opportunities of using stereotactic body radiotherapy with anti-angiogenesis agents in tumor therapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2018Article
- Synthesis and Evaluation of Radiolabeled Phosphoramide Mustard with Selectivity for Hypoxic Cancer Cells.ACS medicinal chemistry letters · 2017Article
- The hypoxia-activated prodrug evofosfamide in combination with multiple regimens of radiotherapy.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundHuman sarcomas with a poor response to vascular endothelial growth factor-A (VEGF-A) inhibition and radiation therapy (RT) have upregulation of hypoxia-inducible factor 1α (HIF-1α) and HIF-1α target genes. This study examines the addition of the hypoxia-activated chemotherapy TH-302 to VEGF-A inhibition and RT (a.k.a. trimodality therapy).
methodsTrimodality therapy was examined in two xenograft models and in vitro in tumour endothelial cells and sarcoma cell lines.
resultsIn both mouse models, VEGF-A inhibition and radiation showed greater efficacy than either therapy alone in slowing sarcoma growth. When TH-302 was added, this trimodality therapy completely blocked tumour growth with tumours remaining dormant for over 3 months after cessation of therapy. Trimodality therapy caused 2.6- to 6.2-fold more endothelial cell-specific apoptosis than bimodality therapies, and microvessel density and HIF-1α activity were reduced to 11-13% and 13-20% of control, respectively. When trimodality therapy was examined in vitro, increases in DNA damage and apoptosis were much more pronounced in tumour endothelial cells compared with that in sarcoma cells, especially under hypoxia.
conclusionsThe combination of TH-302, VEGF-A inhibition, and RT is highly effective in preclinical models of sarcoma and is associated with increased DNA damage and apoptosis in endothelial cells and decreased HIF-1α activity.
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Registered trials
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