MD Anderson researchers identify enzyme linked to cancer drug resistance

Researchers at The University of Texas MD Anderson Cancer Center have identified a mechanism that allows cancer cells to selectively produce growth-promoting proteins, such as KRAS, which can lead to resistance against targeted therapies.

The study, published in Nature Cell Biology, focuses on the enzyme METTL13. This enzyme modifies how cellular machinery reads specific genetic instructions, known as codons, to increase the efficiency of protein production. This process is selective rather than a uniform increase across all proteins.

In preclinical models of lung cancer resistant to the KRAS inhibitor sotorasib, reducing METTL13 levels lowered tumor growth and improved response to treatment. Additionally, researchers observed a clinical association where patients with poorer responses to KRAS inhibitors showed higher inferred METTL13 activity. While these findings suggest METTL13 could be a potential therapeutic target, the study remains in the preclinical stage and does not yet establish a new treatment for human patients.