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Updated: Jan 10, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
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Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?

Zirui Dong1,2, Shoukang Li3,2, Mingfeng Li1,2

  • 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

Cancer Drug Resistance (Alhambra, Calif.)
|November 24, 2025
PubMed

Insights

Metastatic renal cell carcinoma (RCC) has poor survival rates. This review explores new strategies to overcome tyrosine kinase inhibitor (TKI) resistance in kidney cancer, focusing on emerging mechanisms and novel therapies.

Area of Science:

  • Oncology
  • Cancer Research

Background:

  • Renal cell carcinoma (RCC) is the most common kidney cancer, often diagnosed at advanced stages.
  • Metastatic RCC has a poor prognosis despite current treatments like tyrosine kinase inhibitors (TKIs).
  • Acquired resistance to TKIs limits their long-term effectiveness in managing kidney cancer.

Purpose of the Study:

  • To review recent advancements (2020-2025) in understanding and overcoming TKI resistance in RCC.
  • To explore novel therapeutic strategies for TKI-resistant kidney cancer.
  • To inform future research and clinical applications for advanced RCC management.

Main Methods:

  • Literature review and analysis of surveillance data from 2020 to 2025.
  • Exploration of emerging mechanisms of TKI resistance in RCC.
  • Evaluation of innovative therapeutic approaches for TKI-resistant kidney cancer.

Main Results:

  • Identified key resistance mechanisms including tumor microenvironment remodeling, metabolic reprogramming, and alternative survival pathway activation.
  • Highlighted promising therapeutic strategies to circumvent TKI resistance.
  • Emphasized the need for personalized, mechanism-driven treatments for advanced RCC.

Conclusions:

  • Advances in understanding TKI resistance are crucial for improving outcomes in metastatic RCC.
  • Novel therapeutic strategies show promise in overcoming resistance.
  • Personalized, mechanism-based approaches are essential for future RCC management.
Keywords:
Tyrosine kinase inhibitors (TKIs)drug resistancerenal cell carcinoma (RCC)

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