REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
This article is part of the Research TopicModulating Epithelial-Mesenchymal Transition within the Tumor Microenvironment for Targeted Cancer TherapyView all articles
Epithelial-mesenchymal transition and sunitinib resistance in Renal Cell Carcinoma: mechanisms and therapeutic strategies
Provisionally accepted
Mingkai Zhang1Yirui Zhang1Fan Shen2Maoli Yan2Pengfei Cheng2Jing Teng2Mengqin Zou2Wendi Yao3Zhifeng Wang3
Wen Li2*- 1CQMU - University of Leicester Joint Institute, Chongqing Medical University, Chongqing, China
- 2Center for Medical Epigenetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
- 3Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, China
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Renal cell carcinoma (RCC) is a prevalent, highly aggressive malignant tumor that affects the urinary system. RCC has a pronounced propensity for metastasis. Despite the widespread use of sunitinib as first-line therapy for advanced RCC, the occurrence of primary and acquired resistance is frequent and presents significant challenges for effective clinical management. Epithelial–mesenchymal transition (EMT) induction is mediated by hypoxia-HIF signaling, chronic inflammatory stimulation, stromal-tumor cell interactions, and metabolic reprogramming, which confers increased cellular plasticity, migratory potential, and survival benefits. EMT activation is closely associated with reorganization of cellular signaling networks under tumor microenvironment stress, the initiation of alternative angiogenic pathways, and the enhanced anti-apoptotic capacity, all of which contribute to the development of sunitinib resistance. This review systematically summarizes current evidence involving the molecular basis of EMT-driven sunitinib resistance in RCC and investigates potential therapeutic targets, establishing a conceptual foundation for the development of novel strategies to counteract resistance and enhance clinical efficacy.
Keywords: Drug Resistance, Epithelial-Mesenchymal Transition, Renal cell carcinoma, Sunitinib, therapeutic strategies
Received: 05 Dec 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Zhang, Zhang, Shen, Yan, Cheng, Teng, Zou, Yao, Wang and Li. 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: Wen Li
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