ArticleBlood2015
AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy.Frontiers in oncology · 2021Pooled it
- Tumour hypoxia in clinical oncology: imaging, therapeutic strategies, and translational challenges.Clinical and translational radiation oncology · 2027Review
- Rationally designed BCR-ABL kinase inhibitors for improved leukemia treatment via covalent and pro-/dual-drug targeting strategies.Journal of advanced research · 2025Article
- AKR1C3 enhances radioresistance in esophageal adenocarcinoma via inhibiting ferroptosis through suppressing TRIM21-mediated ubiquitination of HSPA5.Cell death & disease · 2025Article
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
- The third generation AKR1C3-activated prodrug, ACHM-025, eradicates disease in preclinical models of aggressive T-cell acute lymphoblastic leukemia.Blood cancer journal · 2024Article
- In vivo activity of the second-generation proteasome inhibitor ixazomib against pediatric T-cell acute lymphoblastic leukemia xenografts.Experimental hematology · 2024Article
- AKR1C3 in carcinomas: from multifaceted roles to therapeutic strategies.Frontiers in pharmacology · 2024Review
- Possible New Histological Prognostic Index for Large B-Cell Lymphoma.Journal of clinical medicine · 2023Article
- A novel ferroptosis-related gene signature for predicting prognosis in multiple myeloma.Frontiers in oncology · 2023Article
- Nitroreduction: A Critical Metabolic Pathway for Drugs, Environmental Pollutants, and Explosives.Chemical research in toxicology · 2022Review
- AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker.Scientific reports · 2022Article
- Analogues of Natural Chalcones as Efficient Inhibitors of AKR1C3.Metabolites · 2022Article
- Therapeutic Targeting of the Leukaemia Microenvironment.International journal of molecular sciences · 2021Review
- Design, synthesis and biological evaluations of a long-acting, hypoxia-activated prodrug of fasudil, a ROCK inhibitor, to reduce its systemic side-effects.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- A novel selective AKR1C3-activated prodrug AST-3424/OBI-3424 exhibits broad anti-tumor activity.American journal of cancer research · 2021Article
- The Complexity of the Tumor Microenvironment and Its Role in Acute Lymphoblastic Leukemia: Implications for Therapies.Frontiers in oncology · 2021Review
- Reversal of Apalutamide and Darolutamide Aldo-Keto Reductase 1C3-Mediated Resistance by a Small Molecule Inhibitor.ACS chemical biology · 2020Article
- Article
- OBI-3424, a Novel AKR1C3-Activated Prodrug, Exhibits Potent Efficacy against Preclinical Models of T-ALL.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
Abstract
PR-104, a phosphate ester of the nitrogen mustard prodrug PR-104A, has shown evidence of efficacy in adult leukemia clinical trials. Originally designed to target hypoxic cells, PR-104A is independently activated by aldo-keto-reductase 1C3 (AKR1C3). The aim of this study was to test whether AKR1C3 is a predictive biomarker of in vivo PR-104 sensitivity. In a panel of 7 patient-derived pediatric acute lymphoblastic leukemia (ALL) xenografts, PR-104 showed significantly greater efficacy against T-lineage ALL (T-ALL) than B-cell-precursor ALL (BCP-ALL) xenografts. Single-agent PR-104 was more efficacious against T-ALL xenografts compared with a combination regimen of vincristine, dexamethasone, and l-asparaginase. Expression of AKR1C3 was significantly higher in T-ALL xenografts compared with BCP-ALL, and correlated with PR-104/PR-104A sensitivity in vivo and in vitro. Overexpression of AKR1C3 in a resistant BCP-ALL xenograft resulted in dramatic sensitization to PR-104 in vivo. Testing leukemic blasts from 11 patients confirmed that T-ALL cells were more sensitive than BCP-ALL to PR-104A in vitro, and that sensitivity correlated with AKR1C3 expression. Collectively, these results indicate that PR-104 shows promise as a novel therapy for relapsed/refractory T-ALL, and that AKR1C3 expression could be used as a biomarker to select patients most likely to benefit from such treatment in prospective clinical trials.
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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.