Amino acid metabolic reprogramming in clear cell renal cell carcinoma: Pathogenic mechanisms and therapeutic...

Area of Science:

• Oncology
• Metabolic pathways
• Cancer biology

Background:

• Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer subtype with significant global health impact.
• While glucose and lipid metabolism changes are known, amino acid metabolism dysregulation in ccRCC is increasingly recognized.

Purpose of the Study:

• To explore the rewiring of amino acid metabolism in ccRCC.
• To identify metabolic dependencies and potential therapeutic targets arising from these alterations.

Main Methods:

• Review and analysis of metabolic pathways in ccRCC.
• Identification of key enzymes and metabolic dependencies.

Main Results:

• Extensive rewiring observed in pathways involving glutamine, cystine, serine, glycine, branched-chain amino acids, methionine, aspartate, arginine, proline, and tryptophan.
• Metabolic alterations support cancer cell proliferation, biosynthesis, redox balance, immune evasion, and therapy resistance.
• Identified dependencies include glutamine and cystine addiction, and arginine auxotrophy.
• Dysregulation of enzymes like GLS1, ASS1, and IDO1 are highlighted.

Conclusions:

• Amino acid metabolism reprogramming in ccRCC creates vulnerabilities that can be exploited therapeutically.
• Targeting metabolic dependencies, such as glutamine and cystine addiction, holds promise for ccRCC treatment.
• Combination therapies involving metabolic inhibitors may overcome resistance and improve patient outcomes.