Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies

Renal cell carcinoma (RCC) is one of the most frequent urological tumors and exhibits metabolic reprogramming alongside genetic mutations. RCC cells reprogram pathways involved in glucose, lipid, and amino acid metabolism to meet their energy and anabolic demands. In recent years, targeted drugs, immunotherapy, and radiotherapy have significantly improved the prognosis of patients with metastatic RCC. Nevertheless, the development of resistance remains a major cause of treatment failure and disease progression in metastatic RCC. A deeper understanding of the metabolic mechanisms underlying therapy resistance is critical for refining therapeutic strategies. The molecular mechanism of metabolic reprogramming involved in therapy resistance is comprehensively discussed. Novel strategies for overcoming therapy resistance of RCC are proposed, including the development of new drugs targeting metabolism, nanoparticles co-loaded with anti-tumor drugs, the application of combination therapies, and personalized medicine approaches. In conclusion, this review provides a thorough overview of metabolic alterations in RCC and their role in therapy resistance, highlighting the potential for developing new treatments for RCC.