Evidence map›Paper›PMID 26025324›Full record

ArticleJournal of the National Cancer Institute2015

Carboxylesterase 2 as a Determinant of Response to Irinotecan and Neoadjuvant FOLFIRINOX Therapy in Pancreatic Ductal Adenocarcinoma.

Michela Capello, Minhee Lee, Hong Wang, Ingrid Babel, Matthew H Katz, Jason B Fleming, Anirban Maitra, Huamin Wang, Weihua Tian, Ayumu Taguchi and 1 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04281511 (A Longitudinal, Observational Biomarker Study in Pancreatic Cancer Patients Receiving Chemotherapy), which is not on this map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

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.

2 · The registry

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.

NCT04281511 completednot on this mapstarted 2019, after this paper: background citation

A Longitudinal, Observational Biomarker Study in Pancreatic Cancer Patients Receiving Chemotherapy

Typeobservational_patient_registrySponsorNational Cancer Center, KoreaRan2019 to 2023Enrolled238ConditionsPancreatic Cancer
3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 104 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Michela Capello: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Minhee Lee: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Hong Wang: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Ingrid Babel: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Matthew H Katz: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Jason B Fleming: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Anirban Maitra: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Huamin Wang: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Weihua Tian: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Ayumu Taguchi: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX.
Samir M Hanash: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (MC, HW, SMH); Fred Hutchinson Cancer Research Center, Seattle, WA (ML, IB); Departments of Surgical Oncology (MHK, JBF), Pathology (AM, HW, WT), and Translational Molecular Pathology (AM, HW, AT, SMH), The University of Texas MD Anderson Cancer Center, Houston, TX. shanash@mdanderson.org.
Fred Hutch Cancer Center · USThe University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Early Diagnosis of Pancreatic CancerU01CA111294 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., HOLLINGSWORTH, MICHAEL A. · 2004 to 2015
$7.1M
NCI NIH HHS U01 CA111294
6 · The paper itself

Abstract

backgroundSerine hydrolases (SHs) are among the largest classes of enzymes in humans and play crucial role in many pathophysiological processes of cancer. We have undertaken a comprehensive proteomic analysis to assess the differential expression and cellular localization of SHs, which uncovered distinctive expression of Carboxylesterase 2 (CES2), the most efficient carboxyl esterase in activating the prodrug irinotecan into SN-38, in pancreatic ductal adenocarcinoma (PDAC). We therefore assessed the extent of heterogeneity in CES2 expression in PDAC and its potential relevance to irinotecan based therapy.

methodsCES2 expression in PDAC and paired nontumor tissues was evaluated by immunohistochemistry. CES2 activity was assessed by monitoring the hydrolysis of the substrate p-NPA and correlated with irinotecan IC50 values by means of Pearson's correlation. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and CES2 expression in patients who underwent neoadjuvant FOLFIRINOX treatment. All statistical tests were two-sided.

resultsStatistically significant overexpression of CES2, both at the mRNA and protein levels, was observed in PDAC compared with paired nontumor tissue (P < .001), with 48 of 118 (40.7%) tumors exhibiting high CES2 expression. CES2 activity in 11 PDAC cell lines was inversely correlated with irinotecan IC50 values (R = -0.68, P = .02). High CES2 expression in tumor tissue was associated with longer overall survival in resectable and borderline resectable patients who underwent neoadjuvant FOLFIRINOX treatment (hazard ratio = 0.14, 95% confidence interval = 0.04 to 0.51, P = .02).

conclusionOur findings suggest that CES2 expression and activity, by mediating the intratumoral activation of irinotecan, is a contributor to FOLFIRINOX sensitivity in pancreatic cancer and CES2 assessment may define a subset of patients likely to respond to irinotecan based therapy.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsCamptothecinCarboxylesteraseCarcinoma, Pancreatic DuctalCell Line, TumorChemotherapy, AdjuvantFemaleFluorouracilHumansImmunohistochemistryIrinotecanKaplan-Meier EstimateMaleMass SpectrometryCamptothecinCarboxylesteraseCES2 protein, humanFluorouracilIrinotecanOrganoplatinum CompoundsOxaliplatinRNA, Messenger

Identifiers

PMID26025324
PMCPMC4554193
OpenAlexW2227346470

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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.