REVIEW article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1702720
This article is part of the Research TopicAdvancements in Solid Tumor Immunotherapy: Enhancing Efficacy and Overcoming ResistanceView all 8 articles
Clinical Application and Drug Resistance Mechanism of Gemcitabine
Provisionally accepted- North China University of Science and Technology, Tangshan, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Gemcitabine, as a nucleoside analog, exerts a broad-spectrum antitumor effect by interfering with DNA synthesis, but its clinical application is limited by drug resistance. The drug resistance mechanism involves metabolic abnormalities (such as downregulation of deoxycytidine kinase (dCK), nucleoside transporter hENT1 deficiency), enhanced DNA repair (overexpression of ribonucleotide reductase ribonucleotide reductase catalytic subunit M1 (RRM1)/ ribonucleotide reductase catalytic subunit M2 (RRM2), and tumor microenvironment remodeling (such as secretion of immunosuppressive factors by CAFs). This article systematically reviews the drug resistance mechanism of gemcitabine and explores the breakthrough direction of new drug delivery systems (liposomes, albumin nanoparticles) and combination therapy strategies (targeted drugs, immune checkpoint inhibitors). In addition, cutting-edge technologies such as single-cell sequencing and artificial intelligence drug sensitivity prediction provide a new paradigm for precision treatment. In the future, it is necessary to build a "prevention-monitoring-intervention" full-chain management system through dynamic monitoring of multi-omics biomarkers (such as circulating tumor DNA tracking RRM2 amplification) and coordinated intervention of traditional Chinese and Western medicine (such as curcumin reversing drug resistance).
Keywords: gemcitabine, Resistance mechanism, Tumor Microenvironment, combination therapy, precision medicine
Received: 10 Sep 2025; Accepted: 20 Oct 2025.
Copyright: © 2025 Zhang, Qi and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jing Chen, chenjing@ncst.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.