ArticlePloS one2014
Evaluation of the "steal" phenomenon on the efficacy of hypoxia activated prodrug TH-302 in pancreatic cancer.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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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
19 citing papers in PubMed, 31 citations in OpenAlex.
- Targeting stromal components in pancreatic ductal adenocarcinoma: a review.Ecancermedicalscience · 2025Review
- Strategies for Pancreatic Cancer-Responsive Nanodrug Platforms Targeting Tumor Hypoxic Environments.International journal of nanomedicine · 2025Review
- Pharmacological Ascorbate Induces Transient Hypoxia Sensitizing Pancreatic Ductal Adenocarcinoma to a Hypoxia Activated Prodrug.bioRxiv : the preprint server for biology · 2024Article
- Exploring chronic and transient tumor hypoxia for predicting the efficacy of hypoxia-activated pro-drugs.NPJ systems biology and applications · 2024Article
- Ultrafast DCE-MRI for discriminating pregnancy-associated breast cancer lesions from lactation related background parenchymal enhancement.European radiology · 2023Article
- Evofosfamide and Gemcitabine Act Synergistically in Pancreatic Cancer Xenografts by Dual Action on Tumor Vasculature and Inhibition of Homologous Recombination DNA Repair.Antioxidants & redox signaling · 2023Article
- Hydralazine-augmented contrast ultrasound imaging improves the detection of hepatocellular carcinoma.Medical physics · 2023Article
- Contrast-enhanced ultrasound for assessing blood flow modulation of hepatocellular carcinoma by hydralazine.IEEE International Ultrasonics Symposium : [proceedings]. IEEE International Ultrasonics Symposium · 2022Article
- Review
- Hydralazine augmented ultrasound hyperthermia for the treatment of hepatocellular carcinoma.Scientific reports · 2021Article
- Overcoming the Tumor Microenvironmental Barriers of Pancreatic Ductal Adenocarcinomas for Achieving Better Treatment Outcomes.Advanced therapeutics · 2021Article
- Targeting hypoxic tumor microenvironment in pancreatic cancer.Journal of hematology & oncology · 2021Review
- The Hypoxia-Activated Prodrug TH-302: Exploiting Hypoxia in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Stroma-Targeting Therapy in Pancreatic Cancer: One Coin With Two Sides?Frontiers in oncology · 2020Review
- Imaging of glucose metabolism by 13C-MRI distinguishes pancreatic cancer subtypes in mice.eLife · 2019Article
- Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials.Clinical and translational radiation oncology · 2019Article
- The Paradoxical Web of Pancreatic Cancer Tumor Microenvironment.The American journal of pathology · 2019Review
- Radiotherapy Synergizes with the Hypoxia-Activated Prodrug Evofosfamide: In Vitro and In Vivo Studies.Antioxidants & redox signaling · 2018Article
- Value of combining dynamic contrast enhanced ultrasound and optoacoustic tomography for hypoxia imaging.Photoacoustics · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinomas are desmoplastic and hypoxic, both of which are associated with poor prognosis. Hypoxia-activated prodrugs (HAPs) are specifically activated in hypoxic environments to release cytotoxic or cytostatic effectors. TH-302 is a HAP that is currently being evaluated in a Phase III clinical trial in pancreatic cancer. Using animal models, we show that tumor hypoxia can be exacerbated using a vasodilator, hydralazine, improving TH-302 efficacy. Hydralazine reduces tumor blood flow through the "steal" phenomenon, in which atonal immature tumor vasculature fails to dilate in coordination with normal vasculature. We show that MIA PaCa-2 tumors exhibit a "steal" effect in response to hydralazine, resulting in decreased tumor blood flow and subsequent tumor pH reduction. The effect is not observed in SU.86.86 tumors with mature tumor vasculature, as measured by CD31 and smooth muscle actin (SMA) immunohistochemistry staining. Combination therapy of hydralazine and TH-302 resulted in a reduction in MIA PaCa-2 tumor volume growth after 18 days of treatment. These studies support a combination mechanism of action for TH-302 with a vasodilator that transiently increases tumor hypoxia.
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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.