Scientists uncover enzyme-driven mechanism that boosts cancer protein production
Researchers at MD Anderson Cancer Center identified a previously unknown pathway involving the METTL13 enzyme that enhances the synthesis of key cancer-promoting proteins like KRAS. This process involves methylation of a translation-related protein, enabling cancer cells to efficiently produce growth-driving proteins despite genetic and metabolic barriers. Targeting this enzyme could potentially improve the effectiveness of existing therapies and reduce treatment resistance.
Researchers at the University of Texas MD Anderson Cancer Center have identified a novel enzyme-driven mechanism involving METTL13 that enhances the production of cancer-promoting proteins such as KRAS in lung and pancreatic cancers. Published in Nature Cell Biology on November 1, 2026, the study reveals that METTL13 methylates the translation factor eEF1A at lysine 55 (eEF1AK55me2), enabling more efficient decoding of mRNA codons—particularly those rich in rare or difficult-to-translate sequences. This selective enhancement allows cancer cells to overcome structural and metabolic barriers to protein synthesis, boosting levels of key oncoproteins without increasing global translation. In preclinical models, knocking down METTL13 reduced KRAS and other oncogenic proteins, slowed tumor growth, and restored sensitivity to the KRAS inhibitor sotorasib in resistant lung cancers, significantly extending survival. Patients with higher METTL13 activity in their tumors also showed poorer responses to therapy, suggesting a clinical link to treatment resistance.
The discovery builds on decades of research into KRAS-driven cancers, which remain difficult to treat despite recent advances in targeted inhibitors. While current drugs like sotorasib block already-produced KRAS protein, this work points to an earlier intervention point—limiting the very production of the oncogenic protein. The team, led by Pawel Mazur, Ph.D., and including Shuo Liu as first author, aims to develop strategies
This discovery could reshape treatment strategies for KRAS-mutant cancers, which account for a significant portion of lung and pancreatic malignancies and have historically been considered “undruggable.” If validated in humans, targeting METTL13 may allow clinicians to prevent oncogenic protein accumulation before it drives tumor progression or resistance—potentially improving outcomes for patients who currently face limited options. The approach may also influence drug development pipelines, encouraging investment in translation-targeted therapies rather than solely focusing on post-translational inhibitors. A comparable precedent is the development of BCL-2 inhibitors in leukemia, which shifted treatment paradigms by targeting a key survival protein earlier in the disease process. However, unlike those drugs, METTL13 inhibition may affect global protein synthesis, raising concerns about toxicity and side effects. The broader impact could extend to diagnostics, with METTL13 levels pot