METTL13 enzyme drives KRAS overproduction and drug resistance

Researchers at MD Anderson and St. Jude found that METTL13 methylates eEF1A at lysine 55, removing a translational brake on KRAS and fueling resistance to sotorasib and adagrasib. Knocking out METTL13 restored treatment sensitivity in resistant lung cancer models without toxicity to normal cells.

• METTL13 methylates eEF1A at lysine 55, lifting the brake on KRAS translation
• METTL13 knockout restored sotorasib sensitivity in cells and mice
• METTL13 activity correlates with poor prognosis in patients
• METTL13 knockout showed no toxicity in C. elegans models