ArticleNature medicine2016
CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.
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Who cites it
116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 226 citations in OpenAlex.
- Machine-Learning-Based Bibliometric Analysis of Pancreatic Cancer Research Over the Past 25 Years.Frontiers in oncology · 2022Pooled it
- Identification of a robust functional subpathway signature for pancreatic ductal adenocarcinoma by comprehensive and integrated analyses.Cell communication and signaling : CCS · 2020Pooled it
- Metabolic characterization of the tumor microenvironment orchestrates therapeutic strategies and clinical outcomes in pancreatic cancer.Nature communications · 2026Article
- A humanized LIF-targeting antibody synergistically enhances chemo- and immunotherapy in pancreatic cancer.Journal of translational medicine · 2026Article
- Article
- Current Advances in Preclinical Patient-Derived Cultivation Models for Individualized Drug Response Prediction in Pancreatic Cancer.Oncology research · 2026Review
- Validation of a UPLC-MS/MS Method for Quantifying Intracellular Olaparib Levels in Resistant Ovarian Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Long non-coding RNA LINC02499 regulates the expression of CYP3A5 in human liver cells.Archives of toxicology · 2025Article
- Targeting pregnane X receptor with a potent agonist-based PROTAC to delay colon cancer relapse.Oncogenesis · 2025Article
- Importance of landscape exploration and progress in molecular therapies and precision medicine for pancreatic ductal adenocarcinoma.World journal of gastrointestinal oncology · 2025Review
- Enhanced mutanome analysis towards the induction of neoepitope-reactive T-cell responses for personalized immunotherapy of pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- Therapy-induced senescence is a transient drug resistance mechanism in breast cancer.Molecular cancer · 2025Article
- Article
- Single-cell analysis reveals that GFAPCell death & disease · 2025Article
- The Prognostic, Predictive and Clinicopathological Implications of KRT81/HNF1A- and GATA6-Based Transcriptional Subtyping in Pancreatic Cancer.Biomolecules · 2025Article
- Multiplexed glycan immunofluorescence identification of pancreatic cancer cell subpopulations in both tumor and blood samples.Science advances · 2025Article
- CYP3A5 promotes glioblastoma stemness and chemoresistance through fine-tuning NADJournal of experimental & clinical cancer research : CR · 2025Article
- Pancreatic cancer subtyping - the keystone of precision treatment.Frontiers in immunology · 2025Review
- Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1-HER3 signaling.Nature cancer · 2025Article
- Dual and triple gene combinations of KRT5, KRT17, and S100A2 identify basal-like subtype of pancreatic ductal adenocarcinoma and correlate with survival outcome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
56 more citing papers are in PubMed but not listed here.
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30 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and identify two markers--HNF1A and KRT81--that enable stratification of tumors into different subtypes by using immunohistochemistry. Individuals with tumors of these subtypes showed substantial differences in overall survival, and their tumors differed in drug sensitivity, with the exocrine-like subtype being resistant to tyrosine kinase inhibitors and paclitaxel. Cytochrome P450 3A5 (CYP3A5) metabolizes these compounds in tumors of the exocrine-like subtype, and pharmacological or short hairpin RNA (shRNA)-mediated CYP3A5 inhibition sensitizes tumor cells to these drugs. Whereas hepatocyte nuclear factor 4, alpha (HNF4A) controls basal expression of CYP3A5, drug-induced CYP3A5 upregulation is mediated by the nuclear receptor NR1I2. CYP3A5 also contributes to acquired drug resistance in QM-PDA and classical PDAC, and it is highly expressed in several additional malignancies. These findings designate CYP3A5 as a predictor of therapy response and as a tumor cell-autonomous detoxification mechanism that must be overcome to prevent drug resistance.
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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.