Newly discovered pathway fuels production of cancer-driving proteins

Research from The University of Texas MD Anderson Cancer Center has identified a previously unknown mechanism that allows cancer cells to selectively produce proteins that drive tumor growth. Published in Nature Cell Biology, the study reveals that the enzyme METTL13 plays a key role in this process, particularly in enhancing the production of KRAS and other cancer-driving proteins.

KRAS is a common mutation found in various types of cancer, including lung and pancreatic cancers, and although targeted therapies have improved outcomes for some patients, tumors often develop resistance over time. The researchers discovered that METTL13 adds a small chemical tag, known as methylation, to a protein involved in protein production.

This modification helps cancer cells read the genetic instructions (codons) more efficiently, leading to increased production of proteins that promote tumor growth. Importantly, METTL13 selectively enhances the production of only a subset of cancer-promoting proteins, rather than broadly increasing the production of all proteins.

By reducing or removing METTL13, the study found that tumor growth was slowed and treatment sensitivity was restored in several preclinical cancer models, including KRAS-mutant lung cancer models that had developed resistance to the KRAS inhibitor sotorasib. These findings suggest that targeting METTL13 may help improve responses to KRAS inhibitors and overcome treatment resistance.

The researchers are working to further understand how METTL13 controls protein production and to develop safe strategies for targeting this enzyme. While these results are preclinical and require further validation, they hold promise for the development of new therapeutic approaches to combat cancer.