WCN26-6423 Pemigatinib-Associated Calciphylaxis versus Calcinosis Cutis in Metastatic Cholangiocarcinoma

metabolic activity and nutrient dependence, to evaluate the metabolic impact of SGLT2 inhibition.Multivariate statistical analyses (PCA, PLS-DA, OPLS-DA) were conducted to identify significantly altered metabolites, which were further subjected to pathway enrichment and network to delineate global metabolic rewiring.Functional validation of pathway-specific alterations was performed through western blotting of key metabolic enzymes.Results: SGLT2 inhibition induced biphasic metabolic remodeling.Early responses involved activation of fatty acid oxidation (FAO) and the urea cycle, with elevated acetyl-CoA, acylcarnitines, and ketone bodies, accompanied by transient AMPK and PGC-1 activation.Later phases showed sustained upregulation of tricarboxylic acid (TCA) cycle intermediates, nucleotide biosynthesis, and one-carbon metabolism, indicating enhanced mitochondrial function and redox balance restoration.In contrast, lipid and glycine-serine metabolism declined, suggesting reduced mTOR activity and impaired membrane turnover.Conclusion: SGLT2 inhibition orchestrates coordinated metabolic and signaling reprogramming in VHL-wildtype RCC, shifting energy metabolism toward oxidative balance and growth suppression.These findings provide mechanistic insights into the anticancer potential of SGLT2 inhibitors and support their repositioning as metabolicsignaling modulators for targeted therapy in renal cancer.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.