hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA

Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering...

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Autores principales:	Karen Aughton, Nils O. Elander, Anthony Evans, Richard Jackson, Fiona Campbell, Eithne Costello, Christopher M. Halloran, John R. Mackey, Andrew G. Scarfe, Juan W. Valle, Ross Carter, David Cunningham, Niall C. Tebbutt, David Goldstein, Jennifer Shannon, Bengt Glimelius, Thilo Hackert, Richard M. Charnley, Alan Anthoney, Markus M. Lerch, Julia Mayerle, Daniel H. Palmer, Markus W. Büchler, Paula Ghaneh, John P. Neoptolemos, William Greenhalf
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	5-fluorouracil gemcitabine pyrimidine biomarker predictive marker prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/bb1597d4958c4fa18c250f0a286270cc
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spelling	oai:doaj.org-article:bb1597d4958c4fa18c250f0a286270cc2021-11-25T17:03:41ZhENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA10.3390/cancers132257582072-6694https://doaj.org/article/bb1597d4958c4fa18c250f0a286270cc2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5758https://doaj.org/toc/2072-6694Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (<i>p =</i> 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (<i>p =</i> 0.02) and 26.4 v 14.6 months with 5-FU (<i>p =</i> 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient.Karen AughtonNils O. ElanderAnthony EvansRichard JacksonFiona CampbellEithne CostelloChristopher M. HalloranJohn R. MackeyAndrew G. ScarfeJuan W. ValleRoss CarterDavid CunninghamNiall C. TebbuttDavid GoldsteinJennifer ShannonBengt GlimeliusThilo HackertRichard M. CharnleyAlan AnthoneyMarkus M. LerchJulia MayerleDaniel H. PalmerMarkus W. BüchlerPaula GhanehJohn P. NeoptolemosWilliam GreenhalfMDPI AGarticle5-fluorouracilgemcitabinepyrimidinebiomarkerpredictive markerprognostic markerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5758, p 5758 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	5-fluorouracil gemcitabine pyrimidine biomarker predictive marker prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	5-fluorouracil gemcitabine pyrimidine biomarker predictive marker prognostic marker Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Karen Aughton Nils O. Elander Anthony Evans Richard Jackson Fiona Campbell Eithne Costello Christopher M. Halloran John R. Mackey Andrew G. Scarfe Juan W. Valle Ross Carter David Cunningham Niall C. Tebbutt David Goldstein Jennifer Shannon Bengt Glimelius Thilo Hackert Richard M. Charnley Alan Anthoney Markus M. Lerch Julia Mayerle Daniel H. Palmer Markus W. Büchler Paula Ghaneh John P. Neoptolemos William Greenhalf hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA
description	Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (<i>p =</i> 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (<i>p =</i> 0.02) and 26.4 v 14.6 months with 5-FU (<i>p =</i> 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient.
format	article
author	Karen Aughton Nils O. Elander Anthony Evans Richard Jackson Fiona Campbell Eithne Costello Christopher M. Halloran John R. Mackey Andrew G. Scarfe Juan W. Valle Ross Carter David Cunningham Niall C. Tebbutt David Goldstein Jennifer Shannon Bengt Glimelius Thilo Hackert Richard M. Charnley Alan Anthoney Markus M. Lerch Julia Mayerle Daniel H. Palmer Markus W. Büchler Paula Ghaneh John P. Neoptolemos William Greenhalf
author_facet	Karen Aughton Nils O. Elander Anthony Evans Richard Jackson Fiona Campbell Eithne Costello Christopher M. Halloran John R. Mackey Andrew G. Scarfe Juan W. Valle Ross Carter David Cunningham Niall C. Tebbutt David Goldstein Jennifer Shannon Bengt Glimelius Thilo Hackert Richard M. Charnley Alan Anthoney Markus M. Lerch Julia Mayerle Daniel H. Palmer Markus W. Büchler Paula Ghaneh John P. Neoptolemos William Greenhalf
author_sort	Karen Aughton
title	hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA
title_short	hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA
title_full	hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA
title_fullStr	hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA
title_full_unstemmed	hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA
title_sort	hent1 predicts benefit from gemcitabine in pancreatic cancer but only with low cda mrna
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bb1597d4958c4fa18c250f0a286270cc
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hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA

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