Deleted Journal, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13
Published: May 20, 2025
Clear cell renal carcinoma (ccRCC), the predominant subtype of kidney cancer, is characterized by extensive metabolic reprogramming driven genetic alterations, notably Von Hippel-Lindau tumor suppressor (VHL) mutations. This reprogrammed glucose, lipid, and amino acid metabolism, exemplified Warburg effect, lipid droplet accumulation, glutamine addiction, to support proliferation, survival, immune evasion. The microenvironment (TME), including hypoxic conditions, tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), further amplifies these shifts, promoting angiogenesis, suppression, progression. Clinically, targeting has shown promise, with hypoxia-inducible factor 2α (HIF-2α) inhibitors like belzutifan achieving FDA approval in 2023 for advanced ccRCC. Glutaminase inhibitors, such as telaglenastat, demonstrate context-dependent efficacy, while indoleamine 2,3-dioxygenase (IDO1) emerging chimeric antigen receptor-engineered (CAR) T-cell therapies ADI-270 offer potential combination strategies. Challenges include heterogeneity, resistance, therapy accessibility. Advances multi-omic profiling biomarker development are paving way personalized treatments. review elucidates mechanisms ccRCC, its interplay TME, clinical applications, highlighting novel therapeutic targets future directions improving patient outcomes.
Language: Английский