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hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status
Gemcitabine is still one of the standard chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine uptake into tumor cells is mainly through the human equilibrative nucleoside transport 1 (hENT1). It was therefore proposed as a potential predictive biomarker of gemcitabine effic...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896053/ https://www.ncbi.nlm.nih.gov/pubmed/31752123 http://dx.doi.org/10.3390/cancers11111808 |
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author | Raffenne, Jerome Nicolle, Remy Puleo, Francesco Le Corre, Delphine Boyez, Camille Marechal, Raphael Emile, Jean François Demetter, Peter Bardier, Armelle Laurent-Puig, Pierre de Mestier, Louis Paradis, Valerie Couvelard, Anne VanLathem, Jean Luc MacKey, John R. Bachet, Jean-Baptiste Svrcek, Magali Cros, Jerome |
author_facet | Raffenne, Jerome Nicolle, Remy Puleo, Francesco Le Corre, Delphine Boyez, Camille Marechal, Raphael Emile, Jean François Demetter, Peter Bardier, Armelle Laurent-Puig, Pierre de Mestier, Louis Paradis, Valerie Couvelard, Anne VanLathem, Jean Luc MacKey, John R. Bachet, Jean-Baptiste Svrcek, Magali Cros, Jerome |
author_sort | Raffenne, Jerome |
collection | PubMed |
description | Gemcitabine is still one of the standard chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine uptake into tumor cells is mainly through the human equilibrative nucleoside transport 1 (hENT1). It was therefore proposed as a potential predictive biomarker of gemcitabine efficacy but reports are conflicting, with an important heterogeneity in methods to assess hENT1 expression. A multicenter cohort of 471 patients with a resected PDAC was used to assess simultaneously the predictive value of the 2 best described hENT1 antibodies (10D7G2 and SP120). Three additional antibodies and the predictive value of hENT1 mRNA were also tested on 251 and 302 patients, respectively. hENT1 expression was assessed in 54 patients with matched primary tumors and metastases samples. The 10D7G2 clone was the only hENT1 antibody whose high expression was associated with a prolonged progression free survival and overall survival in patients who received adjuvant gemcitabine. hENT1 mRNA level was also predictive of gemcitabine benefit. hENT1 status was concordant in 83% of the cases with the best concordance in synchronous metastases. The 10D7G2 clone has the best predictive value of gemcitabine benefit in PDAC patients. Since it is not commercially available, hENT1 mRNA level could represent an alternative to assess hENT1 status. |
format | Online Article Text |
id | pubmed-6896053 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68960532019-12-23 hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status Raffenne, Jerome Nicolle, Remy Puleo, Francesco Le Corre, Delphine Boyez, Camille Marechal, Raphael Emile, Jean François Demetter, Peter Bardier, Armelle Laurent-Puig, Pierre de Mestier, Louis Paradis, Valerie Couvelard, Anne VanLathem, Jean Luc MacKey, John R. Bachet, Jean-Baptiste Svrcek, Magali Cros, Jerome Cancers (Basel) Article Gemcitabine is still one of the standard chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine uptake into tumor cells is mainly through the human equilibrative nucleoside transport 1 (hENT1). It was therefore proposed as a potential predictive biomarker of gemcitabine efficacy but reports are conflicting, with an important heterogeneity in methods to assess hENT1 expression. A multicenter cohort of 471 patients with a resected PDAC was used to assess simultaneously the predictive value of the 2 best described hENT1 antibodies (10D7G2 and SP120). Three additional antibodies and the predictive value of hENT1 mRNA were also tested on 251 and 302 patients, respectively. hENT1 expression was assessed in 54 patients with matched primary tumors and metastases samples. The 10D7G2 clone was the only hENT1 antibody whose high expression was associated with a prolonged progression free survival and overall survival in patients who received adjuvant gemcitabine. hENT1 mRNA level was also predictive of gemcitabine benefit. hENT1 status was concordant in 83% of the cases with the best concordance in synchronous metastases. The 10D7G2 clone has the best predictive value of gemcitabine benefit in PDAC patients. Since it is not commercially available, hENT1 mRNA level could represent an alternative to assess hENT1 status. MDPI 2019-11-18 /pmc/articles/PMC6896053/ /pubmed/31752123 http://dx.doi.org/10.3390/cancers11111808 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Raffenne, Jerome Nicolle, Remy Puleo, Francesco Le Corre, Delphine Boyez, Camille Marechal, Raphael Emile, Jean François Demetter, Peter Bardier, Armelle Laurent-Puig, Pierre de Mestier, Louis Paradis, Valerie Couvelard, Anne VanLathem, Jean Luc MacKey, John R. Bachet, Jean-Baptiste Svrcek, Magali Cros, Jerome hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status |
title | hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status |
title_full | hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status |
title_fullStr | hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status |
title_full_unstemmed | hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status |
title_short | hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status |
title_sort | hent1 testing in pancreatic ductal adenocarcinoma: are we ready? a multimodal evaluation of hent1 status |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896053/ https://www.ncbi.nlm.nih.gov/pubmed/31752123 http://dx.doi.org/10.3390/cancers11111808 |
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