ArticleJCO precision oncology2020
CES2 Expression in Pancreatic Adenocarcinoma Is Predictive of Response to Irinotecan and Is Associated With Type 2 Diabetes.
Article in JCO precision oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- SEOM clinical guidelines for pancreatic and biliary tract cancer (2020).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Guideline
- Article
- Screening of common genomic biomarkers to explore common drugs for the treatment of pancreatic and kidney cancers with type-2 diabetes through bioinformatics analysis.Scientific reports · 2025Article
- Article
- The conjugates of 5'-deoxy-5-fluorocytidine and hydroxycinnamic acids - synthesis, anti-pancreatic cancer activity and molecular docking studies.RSC advances · 2024Article
- Highly Sensitive "Off/On" EPR Probes to Monitor Enzymatic Activity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- CES2 sustains HNF4α expression to promote pancreatic adenocarcinoma progression through an epoxide hydrolase-dependent regulatory loop.Molecular metabolism · 2022Article
- Carboxylesterase 4A Inhibits the Malignant Biological Behavior of Nasopharyngeal Carcinoma via the PI3K/AKT Pathway.Technology in cancer research & treatmentArticle
- Current Treatment of Potentially Resectable Pancreatic Ductal Adenocarcinoma: A Medical Oncologist's Perspective.Cancer control : journal of the Moffitt Cancer CenterReview
Corrections and comments
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Authors and funding
30 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThe combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC.
methodsPDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (HNF4A) expression in PDAC tissues was evaluated by immunohistochemical and Western blot analysis. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and hemoglobin A1C (HbA1C) levels in patients who underwent neoadjuvant FOLFIRINOX treatment.
resultsHigh CES2 activity in PDAC PDXs was associated with increased sensitivity to irinotecan. Integrated gene expression, proteomic analyses, and in vitro genetic experiments revealed that nuclear receptor HNF4A, which is upregulated in diabetes, is the upstream transcriptional regulator of CES2 expression. Elevated CES2 protein expression in PDAC tissues was positively associated with a history of type 2 diabetes (odds ratio, 4.84;
conclusionTo our knowledge, we provide, for the first time, evidence that CES2 expression is associated with a history of type 2 diabetes in PDAC and that elevated HbA1C, by predicting tumor CES2 expression, may represent a novel marker for stratifying patients most likely to respond to FOLFIRINOX therapy.
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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.