Abstract 286: Metabolic alterations in skeletal muscle and serum of tumor-bearing cachectic mice

Abstract Cancer cachexia, a multifactorial syndrome characterized by systemic inflammation, high energy expenditure, and progressive skeletal muscle loss, poses a significant challenge in cancer management due to limited therapeutic options. Understanding the metabolic shifts associated with cachexia-related muscle wasting could provide critical insights into identifying potential biomarkers and therapeutic targets. In this study, we conducted targeted metabolomics to investigate metabolic alterations in the skeletal muscle and serum of tumor-bearing cachectic mice. To facilitate a comprehensive analysis, skeletal muscle samples from non-cachectic tumor-bearing mice were included to explore metabolic changes associated with tumor growth and its progression to cachexia. We found that tumor-bearing, non-cachectic muscles exhibited significantly higher levels of glucose-6-phosphate (G6P), fructose-6-phosphate with glucose-1-phosphate (F6P + G1P), glyceraldehyde-3-phosphate (G3P), glycerol-3-phosphate (Glycerol-3P), and phosphoenolpyruvate (PEP) compared to control muscles. However, no significant differences were observed between non-cachectic muscles and cachectic muscles. These findings indicate that increased glycolysis is more critical for tumor growth than for the progression to cachexia. Amino acids such as asparagine, alanine, and serine were significantly increased in cachectic muscle. Compared to non-cachectic muscle, levels of 2-hydroxyglutarate (2-HG) and CoA were decreased in cachectic skeletal muscle. Notably, alterations in 2-HG and CoA were consistent between muscle and serum, highlighting their potential as systemic biomarkers. These results reveal key metabolic alterations in skeletal muscle and serum associated with cancer cachexia, offering novel insights into the pathogenesis of muscle wasting and providing potential avenues for biomarker discovery and therapeutic intervention. Citation Format: Kuo-Chu Lai. Metabolic alterations in skeletal muscle and serum of tumor-bearing cachectic mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 286.