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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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