ArticleBritish journal of cancer2018
AKR1C enzymes sustain therapy resistance in paediatric T-ALL.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- NRF2 activation is required for chemotherapy resistance acquisition in medulloblastoma via metabolic and redox adaptation.Redox biology · 2026Article
- Role of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia.Nature communications · 2025Article
- Discovery and Optimization of a Covalent AKR1C3 Inhibitor.Journal of medicinal chemistry · 2025Article
- The Role of UFMylation in the Development and Progression of Gastric Cancer.Oncology research · 2025Review
- The third generation AKR1C3-activated prodrug, ACHM-025, eradicates disease in preclinical models of aggressive T-cell acute lymphoblastic leukemia.Blood cancer journal · 2024Article
- Coumarin-Based Aldo-Keto Reductase Family 1C (AKR1C) 2 and 3 Inhibitors.ChemMedChem · 2024Article
- AKR1C4 regulates the sensitivity of colorectal cancer cells to chemotherapy through ferroptosis modulation.Cancer chemotherapy and pharmacology · 2024Article
- Deconstructing Intratumoral Heterogeneity through Multiomic and Multiscale Analysis of Serial Sections.Cancers · 2024Article
- Article
- Discovery of an Aldo-Keto reductase 1C3 (AKR1C3) degrader.Communications chemistry · 2024Article
- Deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial sections.bioRxiv : the preprint server for biology · 2024Article
- Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia.International journal of molecular sciences · 2023Article
- X-ray structure of human aldo-keto reductase 1C3 in complex with a bile acid fused tetrazole inhibitor: experimental validation, molecular docking and structural analysis.RSC medicinal chemistry · 2023Article
- The effect of the alpha-specific PI3K inhibitor alpelisib combined with anti-HER2 therapy in HER2+/PIK3CA mutant breast cancer.Frontiers in oncology · 2023Article
- Comparative Analysis of Coumarin Profiles in Different Parts ofMolecules (Basel, Switzerland) · 2022Article
- Bruton's Tyrosine Kinase Inhibitor Zanubrutinib Effectively Modulates Cancer Resistance by Inhibiting Anthracycline Metabolism and Efflux.Pharmaceutics · 2022Article
- AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker.Scientific reports · 2022Article
- AKR1C1/2 inhibition by MPA sensitizes platinum resistant ovarian cancer towards carboplatin.Scientific reports · 2022Article
- Natural Product Alantolactone Targeting AKR1C1 Suppresses Cell Proliferation and Metastasis in Non-Small-Cell Lung Cancer.Frontiers in pharmacology · 2022Article
- The role of non-coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential.Cancer communications (London, England) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite chemotherapy intensification, a subgroup of high-risk paediatric T-cell acute lymphoblastic leukemia (T-ALL) patients still experience treatment failure. In this context, we hypothesised that therapy resistance in T-ALL might involve aldo-keto reductase 1C (AKR1C) enzymes as previously reported for solid tumors.
methodsExpression of NRF2-AKR1C signaling components has been analysed in paediatric T-ALL samples endowed with different treatment outcomes as well as in patient-derived xenografts of T-ALL. The effects of AKR1C enzyme modulation has been investigated in T-ALL cell lines and primary cultures by combining AKR1C inhibition, overexpression, and gene silencing approaches.
resultsWe show that T-ALL cells overexpress AKR1C1-3 enzymes in therapy-resistant patients. We report that AKR1C1-3 enzymes play a role in the response to vincristine (VCR) treatment, also ex vivo in patient-derived xenografts. Moreover, we demonstrate that the modulation of AKR1C1-3 levels is sufficient to sensitise T-ALL cells to VCR. Finally, we show that T-ALL chemotherapeutics induce overactivation of AKR1C enzymes independent of therapy resistance, thus establishing a potential resistance loop during T-ALL combination treatment.
conclusionsHere, we demonstrate that expression and activity of AKR1C enzymes correlate with response to chemotherapeutics in T-ALL, posing AKR1C1-3 as potential targets for combination treatments during T-ALL therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.