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

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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Detalles Bibliográficos
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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Sumario: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.

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