Metabolic vulnerabilities in Rhabdoid Tumor of Kidney under amino acid-deprivation : A potential Achilles' heel.

Abstract Background Rhabdoid Tumor of the Kidney (RTK) is a rare and highly aggressive pediatric tumor that occurs in infancy and early childhood. Due to limited studies, the involvement of metabolism in RTK’s growth and progression is not completely understood. However, it is well known that nutrient deprivation is an environmental stress factor that can influence cancer cells' behavior, leading to a reprogramming in metabolism. Methods We investigated the metabolic profile of G-401malignant rhabdoid tumor cells under deprivation of various amino acids (AAs) combined an array of complementary techniques, including Seahorse analysis, Western blot, and qRT-PCR. Patient plasma samples were analyzed to determine AAs concentrations using HPLC-MS/MS. Results Our findings highlight metabolic plasticity as a critical mechanism for RTK cell survival. However, this adaptability can be effectively targeted by depriving cells of selected AAs. While Gln deprivation alone or combined with Tyr/Phe increases GLUT1 expression and glucose uptake, it fails to provide sufficient energy for cell survival. This metabolic vulnerability could enhance sensitivity to chemotherapy, thus representing a promising therapeutic strategy through the addition of metabolic inhibitors to current treatments to improve cancer treatment. Conclusion Deprivation in -Tyr/-Phe/-Gln seems to sensitize RTK cells with potential therapeutic implications.