2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.21 Parang

PP01.21 Parang - Abstract

Pdf Summary

A study conducted at Weill Cornell Medicine revealed that elevated levels of methylmalonic acid (MMA), a by-product of propionate metabolism, are associated with non-small cell lung cancer (NSCLC) and correlated with poorer survival rates. The research identified that MMAB, a key regulatory gene for MMA, is downregulated in lung cancer tumors, particularly in never-smokers and patients with EGFR-mutated disease. The study found that lower MMAB levels were linked to worse overall survival and increased resistance to osimertinib, a common treatment for NSCLC. In vitro experiments confirmed that knocking down MMAB led to higher MMA levels, resistance to osimertinib, and activation of epithelial-to-mesenchymal transition (EMT) signaling pathways. This study provides insight into the clinical relevance of dysregulated propionate metabolism in lung cancer, particularly in relation to osimertinib resistance. The findings suggest that targeting MMAB and controlling MMA levels could potentially overcome osimertinib resistance in NSCLC patients.

Keywords

methylmalonic acid

propionate metabolism

non-small cell lung cancer

MMAB gene

EGFR-mutated disease

osimertinib resistance

epithelial-to-mesenchymal transition

lung cancer tumors

clinical relevance

targeting MMAB