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

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5758
Author(s):  
Karen Aughton ◽  
Nils O. Elander ◽  
Anthony Evans ◽  
Richard Jackson ◽  
Fiona Campbell ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cytidine Deaminase ◽  
Nucleoside Transporter ◽  
Treatment Benefit ◽  
Cancer Trial ◽  
Equilibrative Nucleoside Transporter ◽  
Protein Levels ◽  
Protein Status ◽  
The Individual

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 (p = 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (p = 0.02) and 26.4 v 14.6 months with 5-FU (p = 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.

Human Equilibrative Nucleoside Transporter 1 Levels Predict Response to Gemcitabine in Patients With Pancreatic Cancer

2009 ◽  
Vol 136 (1) ◽  
pp. 187-195 ◽  
Author(s):  
James J. Farrell ◽  
Hany Elsaleh ◽  
Miguel Garcia ◽  
Raymond Lai ◽  
Ali Ammar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Nucleoside Transporter ◽  
Equilibrative Nucleoside Transporter

scholarly journals Novel Strategy with Gemcitabine for Advanced Pancreatic Cancer

ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Shuji Komori ◽  
Shinji Osada ◽  
Kazuhiro Yoshida
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Metabolic Enzymes ◽  
Interindividual Variation ◽  
Nucleoside Transporter ◽  
Standard Drug ◽  
Equilibrative Nucleoside Transporter ◽  
Nucleotide Pools ◽  
Novel Strategy

5-fluorouracil (5-FU) is widely used in chemotherapy for gastric and colorectal cancer, but gemcitabine (GEM), and not 5-FU, is approved as a standard drug for use in pancreatic cancer. Interindividual variation in the enzyme activity of the GEM metabolic pathway can affect the extent of GEM metabolism and the efficacy of GEM chemotherapy. Human equilibrative nucleoside transporter 1 (hENT1) is recognized as a major transporter of GEM into cells. In addition, a factor that activates hENT1 is the inhibition of thymidylate synthase (TS), one of the 5-FU metabolic enzymes; TS inhibition mediates depleting intracellular nucleotide pools, resulting in the activation of the salvage pathway mediated through hENT1. In this paper, the role of 5-FU in GEM-based chemotherapy for pancreatic cancer is discussed with special emphasis on enzymes involved in the 5-FU and GEM metabolic pathways and in the correlation between GEM responsiveness and the expression of 5-FU and GEM metabolic enzymes.

Use of human equilibrative nucleoside transporter 1 to predict survival after adjuvant gemcitabine chemotherapy in resected pancreatic adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 224-224
Author(s):  
S. Morinaga ◽  
N. Yamamoto ◽  
M. Shiozawa ◽  
H. Tamagawa ◽  
M. Ueno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Cells ◽  
Pancreatic Adenocarcinoma ◽  
Curative Resection ◽  
Staining Intensity ◽  
Nucleoside Transporter ◽  
Prognostic Information ◽  
Positive Tumor Cell ◽  
Equilibrative Nucleoside Transporter

224 Background: Gemcitabine is a promising adjuvant treatment for patients with resected pancreatic adenocarcinoma. Human equilibrative nucleoside transporter 1 (hENT1) is the major transporter responsible for 2′, 2′-difluoro-2deoxycytidine (gemcitabine) uptake into cells. The aim of this study was to determine the outcomes according to the expression of hENT1 in tumor cells in patients treated with adjuvant gemcitabine chemotherapy after curative resection. Methods: We studied 27 pancreatic adenocarcinoma patients treated with gemcitabine adjuvant chemotherapy after curative resection and 8 gemcitabine naïve patients between 2006 and 2008. The hENT expressions were assessed using immunohistochemistry. The staining intensity of hENT1 protein was assigned a score from 0 to 3 based on staining with 0: no staining, 1: weakly positive, 2: moderately positive, 3: strongly positive. The percentage of positive tumor cells was scored as follows, 0: no positive tumor cell; 1: < 50% positive cells, 2: 51-80% positive cells, 3: > 81% positive cells. The hENT1 score was obtained by calculating the sum of these two scores. Each patients received adjuvant chemotherapy by either protocols as follows; GEM 1,000 mg/m2biweekly × 12 (6 months) or GEM 1,000 mg/m2Days 1,8,15; every 4 weeks for 6 months. Results: 11 patients were assigned to low hENT1 expression group (hENT1 score <4) and 16 patients to high hENT1 group (hENT1 score 4,5,6). The median DFS was 7.3 months (95% CI, 3.6-11.1) in the low hENT1 group, and 9.3 months (95% CI, 4.2-14.5) in the high hENT1 group. The median OS was 11.8 months (95% CI, 6.9- 16.6) in the low hENT1 group, and 22.2 months (95% CI, 11.5-32.9). The high hENT1 group had significantly longer DFS (Log-rank, p=0.04) and OS (p=0.02). In the gemcitabine naïve patients after curative resection, neither DFS nor OS correlated with hENT1 expression. Conclusions: In the pancreatic cancer patients treated with adjuvant gemcitabine chemotherapy after curative resection, both DFS and OS correlated with hENT1 expression. The expression of hENT1 may provides prognostic information and predictive for benefit from gemcitabine in these patients. No significant financial relationships to disclose.

Adenoviral-mediated overexpression of human equilibrative nucleoside transporter 1 (hENT1) enhances gemcitabine response in human pancreatic cancer

2008 ◽  
Vol 76 (3) ◽  
pp. 322-329 ◽  
Author(s):  
Sandra Pérez-Torras ◽  
José García-Manteiga ◽  
Elena Mercadé ◽  
F. Javier Casado ◽  
Neus Carbó ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Human Pancreatic Cancer ◽  
Nucleoside Transporter ◽  
Equilibrative Nucleoside Transporter
Sign in / Sign up

Export Citation Format

Share Document