# Epithelial-mesenchymal transition and sunitinib resistance in renal cell carcinoma: mechanisms and therapeutic strategies

## TL;DR

This paper reviews how EMT contributes to sunitinib resistance in kidney cancer and explores new treatment strategies to overcome this resistance.

## Contribution

The paper systematically summarizes the molecular mechanisms of EMT-driven sunitinib resistance and identifies potential therapeutic targets.

## Key findings

- EMT is linked to sunitinib resistance through hypoxia-HIF signaling and tumor microenvironment stress.
- EMT enhances cell survival and migration, promoting resistance to sunitinib in RCC.
- The review highlights potential therapeutic strategies to counteract EMT-driven resistance.

## Abstract

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.