Abstract 2378: Methylmalonic acid is elevated in non-small cell lung cancer and promotes drug resistance

Lung cancer is the leading cause of cancer-related deaths in the United States. Identifying new factors that promote drug resistance is critical to restoring drug sensitivity and improving patient outcomes. Methylmalonic acid (MMA) is a dicarboxylic acid by-product of propionate metabolism. MMA levels rise in the serum with age and are associated with cancer-related mortality (the higher the MMA, the worse the mortality). We recently asked whether this metabolite had a functional impact and showed that treating non-small cell lung cancer (NSCLC) cells with MMA in vitro promotes drug resistance through triggering epithelial-to-mesenchymal transition (EMT). However, whether MMA is elevated in lung cancer is not known, and how MMA levels are regulated is poorly understood. To determine if MMA is elevated in NSCLC, we performed targeted metabolomics on 20 resected lung adenocarcinomas and squamous cell carcinomas with matched normal lung tissue. We found that MMA was 2.5 fold elevated in tumors compared to controls (p