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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

The final, formatted version of the article will be published soon.

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

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