Targeting Metabolic Pathways in Kidney Cancer: Rationale and Therapeutic Opportunities

Area of Science:

• Oncology
• Cancer Metabolism
• Molecular Biology

Background:

• Renal cell carcinoma (RCC) is characterized by significant alterations in cellular metabolism, including sugar, amino acid, nucleic acid, and lipid pathways, alongside mitochondrial dysfunction.
• Early tumorigenesis in RCC involves oncogene activation (e.g., hypoxia-inducible factor) and tumor suppressor loss (e.g., von Hippel-Lindau), driving metabolic reprogramming that enhances tumor growth, proliferation, and stress resilience.
• Tumor cells can develop dependencies, or addictions, to these reprogrammed metabolic states, presenting potential therapeutic targets.

Purpose of the Study:

• To review current knowledge on metabolic addictions specifically in clear cell renal cell carcinoma (ccRCC).
• To assess the therapeutic opportunities arising from targeting these altered metabolic pathways in ccRCC.
• To provide a comprehensive overview of preclinical and clinical data on novel therapeutics targeting metabolic traits in ccRCC.

Main Methods:

• Literature review of preclinical and clinical studies.
• Analysis of current knowledge on metabolic reprogramming in ccRCC.
• Synthesis of data on therapeutic strategies targeting metabolic vulnerabilities.

Main Results:

• Clear cell RCC exhibits distinct metabolic reprogramming, creating dependencies that can be exploited therapeutically.
• Numerous preclinical and emerging clinical strategies aim to interfere with these altered metabolic pathways.
• Targeting metabolic traits offers a promising avenue for selective tumor cell destruction.

Conclusions:

• Metabolic reprogramming and addiction are critical features of ccRCC.
• Targeting these metabolic vulnerabilities represents a significant and evolving therapeutic strategy for ccRCC.
• Exploiting metabolic reprogramming clinically holds promise for improved ccRCC treatment outcomes.