ArticleClinical and translational radiation oncology2019
Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials.
Article in Clinical and translational radiation oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed.
- Tumour hypoxia in clinical oncology: imaging, therapeutic strategies, and translational challenges.Clinical and translational radiation oncology · 2027Review
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- Why Targeting Tumor Acidity Fails: Translational Barriers and Emerging Solutions.International journal of molecular sciences · 2026Review
- Understanding the Interplay Between Obesity and Cancer: From Mechanisms to Therapeutic Opportunities.Cancers · 2026Review
- Therapeutic embolic agents for targeted drug delivery in transcatheter therapies: a review.Chemical communications (Cambridge, England) · 2026Review
- Deficiencies in the Fanconi anemia or homologous recombination pathway enhance the antitumor effects of the hypoxia-activated prodrug CP-506.Molecular therapy. Oncology · 2026Article
- An oxygen gradient chamber with simple geometry for generating oxygen gradients in hydrogel-based cell cultures within a well-plate-compatible format.Frontiers in bioengineering and biotechnology · 2026Article
- Breast Cancer: Challenges in the Treatment and Prodrug Strategies.Mini reviews in medicinal chemistry · 2026Review
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- Carcinogenesis: An Alternative Hypothesis Comparing Mutagenic Versus Metabolic Models.Biology · 2025Review
- Review
- Atovaquone-induced activation of the PERK/eIF2α signaling axis mitigates metabolic radiosensitisation.Cell communication and signaling : CCS · 2025Article
- Defining hypoxia in cancer: A landmark evaluation of hypoxia gene expression signatures.Cell genomics · 2025Article
- Novel Prodrug Strategies for the Treatment of Tuberculosis.Chemistry, an Asian journal · 2024Review
- Prodrug activation by 4,4'-bipyridine-mediated aromatic nitro reduction.Nature communications · 2024Article
- Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models.Molecular oncology · 2024Article
- Recent Advances in the Application of Nitro(het)aromatic Compounds for Treating and/or Fluorescent Imaging of Tumor Hypoxia.Molecules (Basel, Switzerland) · 2024Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-activated prodrugs (HAPs) are designed to specifically target the hypoxic cells of tumors, which are an important cause of treatment resistance to conventional therapies. Despite promising preclinical and clinical phase I and II results, the most important of which are described in this review, the implementation of hypoxia-activated prodrugs in the clinic has, so far, not been successful. The lack of stratification of patients based on tumor hypoxia status, which can vary widely, is sufficient to account for the failure of phase III trials. To fully exploit the potential of hypoxia-activated prodrugs, hypoxia stratification of patients is needed. Here, we propose a biomarker-stratified enriched Phase III study design in which only biomarker-positive (i.e. hypoxia-positive) patients are randomized between standard treatment and the combination of standard treatment with a hypoxia-activated prodrug. This implies the necessity of a Phase II study in which the biomarker or a combination of biomarkers will be evaluated. The total number of patients needed for both clinical studies will be far lower than in currently used randomize-all designs. In addition, we elaborate on the improvements in HAP design that are feasible to increase the treatment success rates.
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