ArticleCancer letters2015
Hypoxia-activated pro-drug TH-302 exhibits potent tumor suppressive activity and cooperates with chemotherapy against osteosarcoma.
Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy.Frontiers in oncology · 2021Pooled it
- The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma.British journal of cancer · 2018Trial
- 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
- Bimodality imaging as a companion to evaluate antitumour efficacy of TH-302 in experimental chondrosarcoma.EJNMMI research · 2025Article
- Hypoxia-activated selectivity-improved anti-PKM2 antibody combined with prodrug TH-302 for potentiated targeting therapy in hepatocellular carcinoma.International journal of biological sciences · 2024Article
- TH-302-loaded nanodrug reshapes the hypoxic tumour microenvironment and enhances PD-1 blockade efficacy in gastric cancer.Journal of nanobiotechnology · 2023Article
- Article
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
- Mitochondria-targeting multifunctional nanoplatform for cascade phototherapy and hypoxia-activated chemotherapy.Journal of nanobiotechnology · 2022Article
- Positron Emission Tomographic Imaging of Tumor Cell Death Using Zirconium-89-Labeled APOMAB® Following Cisplatin Chemotherapy in Lung and Ovarian Cancer Xenograft Models.Molecular imaging and biology · 2021Article
- Targeting Cellular DNA Damage Responses in Cancer: An In Vitro-Calibrated Agent-Based Model Simulating Monolayer and Spheroid Treatment Responses to ATR-Inhibiting Drugs.Bulletin of mathematical biology · 2021Article
- Perspectives on Hypoxia Signaling in Tumor Stroma.Cancers · 2021Review
- The Hypoxia-Activated Prodrug TH-302: Exploiting Hypoxia in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Osteosarcoma and Metastasis.Frontiers in oncology · 2021Review
- Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients.Journal of nanobiotechnology · 2020Article
- Bone Microenvironment and Osteosarcoma Metastasis.International journal of molecular sciences · 2020Review
- Combining hypoxia-activated prodrugs and radiotherapy in silico: Impact of treatment scheduling and the intra-tumoural oxygen landscape.PLoS computational biology · 2020Article
- 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
- Established Models and New Paradigms for Hypoxia-Driven Cancer-Associated Bone Disease.Calcified tissue international · 2018Review
- Validation of a hypoxia related gene signature in multiple soft tissue sarcoma cohorts.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, tumor hypoxia also offers treatment opportunities, exemplified by the development compounds that target hypoxic regions within tumors. TH-302 is a pro-drug created by the conjugation of 2-nitroimidazole to bromo-isophosphoramide (Br-IPM). When TH-302 is delivered to regions of hypoxia, Br-IPM, the DNA cross linking toxin, is released. In this study we assessed the cytotoxic activity of TH-302 against osteosarcoma cells in vitro and evaluated its anticancer efficacy as a single agent, and in combination with doxorubicin, in an orthotopic mouse model of human osteosarcoma (OS). In vitro, TH-302 was potently cytotoxic to osteosarcoma cells selectively under hypoxic conditions, whereas primary normal human osteoblasts were protected. Animals transplanted with OS cells directly into their tibiae and left untreated developed mixed osteolytic/osteosclerotic bone lesions and subsequently developed lung metastases. TH-302 reduced tumor burden in bone and cooperated with doxorubicin to protect bone from osteosarcoma induced bone destruction, while it also reduced lung metastases. TH-302 may therefore be an attractive therapeutic agent with strong activity as a single agent and in combination with chemotherapy against OS.
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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.