“Open Sesame?”: biomarker status of the human equilibrative nucleoside transporter-1 and molecular mechanisms influencing its expression and activity in the uptake and cytotoxicity of gemcitabine in pancreatic cancer
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive tumor characterized by early invasiveness, rapid progression and resistance to treatment. Gemcitabine has been for more than twenty years the main therapy for PDAC both in the palliative and adjuvant setting. After the introduction of FOLFIRINOX as upfront treatment for metastatic disease, gemcitabine is still commonly used in combination with nab-paclitaxel as an alternative first-line regimen, as well as a monotherapy in elderly patients unfit for combination chemotherapy. As a hydrophilic nucleoside analogue, gemcitabine requires nucleoside transporters to permeate the plasma membrane, and a major role in the uptake of this drug is played by human equilibrative nucleoside transporter 1 (hENT-1). Several studies have proposed hENT-1 as a biomarker for gemcitabine efficacy in PDAC. A recent comprehensive multimodal analysis of hENT-1 status evaluated its predictive role by both immunohistochemistry (with five different antibodies), and quantitative-PCR, supporting the use of the 10D7G2 antibody. High hENT-1 levels observed with this antibody were associated with prolonged disease-free and overall-survival in patients receiving gemcitabine adjuvant chemotherapy. We discuss this analysis and lists molecular factors influencing hENT-1. Improved knowledge on these factors should help in the identification of subgroups of patients who may benefit from specific therapies and overcome the limitations of traditional biomarker studies.
Date Issued
2020-10-31
Date Acceptance
2020-10-26
Citation
Cancers, 2020, 12 (11)
ISSN
2072-6694
Publisher
MDPI AG
Journal / Book Title
Cancers
Volume
12
Issue
11
Copyright Statement
©2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
pancreatic cancer
drug resistance
human equilibrative nucleoside transporter 1
clinical outcome
LEVELS PREDICT RESPONSE
DUCTAL ADENOCARCINOMA
ADJUVANT GEMCITABINE
1 HENT1
SURVIVAL
RESISTANCE
CELLS
ROLES
CHEMOTHERAPY
METASTASIS
clinical outcome
drug resistance
human equilibrative nucleoside transporter 1
pancreatic cancer
1112 Oncology and Carcinogenesis
Publication Status
Published
Article Number
ARTN 3206