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Arginine transport systems, primarily the Cationic Amino Acid Transporters (CATs) belonging to the SLC7 family, mediate the uptake of L-arginine into cells [UniProt P30825]. L-arginine is a versatile amino acid essential for protein synthesis and serves as a precursor for nitric oxide, polyamines, and creatine [PubMed 30154018]. In the context of oncology, many tumors exhibit arginine auxotrophy due to the loss of argininosuccinate synthetase 1 (ASS1), making them dependent on these transport systems for survival [PubMed 27103444]. This dependency creates a therapeutic vulnerability that can be exploited by depleting extracellular arginine or potentially inhibiting the transporters directly [ClinicalTrials.gov NCT02709512]. Beyond cancer, these systems are involved in regulating vascular tone and immune cell activation by controlling the availability of arginine for nitric oxide synthase [PubMed 21169519]. Current clinical approaches primarily utilize arginine-depleting enzymes like pegargiminase to starve tumor cells, while research into direct inhibitors of CAT-1 and related transporters continues as a means to treat both metabolic and inflammatory disorders [PubMed 31431546].
Inhibition of cellular arginine uptake or depletion of extracellular arginine to induce metabolic starvation in arginine-auxotrophic cells.
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