Disturbances in Nitric Oxide Cycle and Related Molecular Pathways in Clear Cell Renal Cell Carcinoma

Simple Summary In this article, we analyze the current state of research on nitric oxide biosynthesis metabolites in clear cell renal cell carcinoma and the metabolic pathways that amplify nitric oxide production in the tumour microenvironment. Special attention is given to nitric oxide homeostasis disruption, mechanisms of nitric oxide biosynthesis and signalling, analysis of nitric oxide bimodal effects, quantitative analysis of nitric oxide, metabolites ureagenic cycle and glutamine metabolism, arginine metabolism and depletion, hyperammonemia, branched-chain amino acids catabolism and nitric oxide-based therapy for cancer. Clarifying these issues will contribute to the development of personalized medicine for patients with clear cell renal carcinoma.Abstract It is important to note that maintaining adequate levels of nitric oxide (NO), the turnover, and the oxidation level of nitrogen are essential for the optimal progression of cellular processes, and alterations in the NO cycle indicate a crucial step in the onset and progression of multiple diseases. Cellular accumulation of NO and reactive nitrogen species in many types of tumour cells is expressed by an increased susceptibility to oxidative stress in the tumour microenvironment. Clear cell renal cell carcinoma (ccRCC) is a progressive metabolic disease in which tumour cells can adapt to metabolic reprogramming to enhance NO production in the tumour space. Understanding the factors governing NO biosynthesis metabolites in ccRCC represents a relevant, valuable approach to studying NO-based anticancer therapy. Exploring the molecular processes mediated by NO, related disturbances in molecular pathways, and NO-mediated signalling pathways in ccRCC could have significant therapeutic implications in managing and treating this condition.