The key facts

  • The enzyme METTL13 adds a chemical tag to a protein of the cell's synthesis machinery, increasing the production of KRAS and other tumor-growth proteins.
  • In preclinical models, suppressing METTL13 slowed tumor growth and restored sensitivity to sotorasib.
  • High METTL13 activity in patients' tumors is associated with a worse response to drugs against KRAS.

A mechanism that accelerates tumor growth

Scientists at The University of Texas MD Anderson Cancer Center have described a mechanism by which cancer cells speed up their own growth. According to Gazeta.Ru, the enzyme METTL13 adds a chemical tag to one of the proteins involved in producing other proteins in the cell. Thanks to this, the cellular machinery reads genetic instructions more efficiently and produces more of certain proteins — including KRAS, which drives the growth of many tumors. The study results were published in the journal Nature Cell Biology.

Why this matters for treatment

The significance of the discovery is tied to the problem of therapy resistance. “The KRAS gene is frequently mutated in lung and pancreatic cancer. Despite the emergence of drugs that block its activity, tumors sometimes adapt to treatment and become resistant to the medications,” the scientists explained. In experiments on preclinical models, reducing METTL13 activity decreased the production of KRAS and other proteins that support cell growth, causing tumors to grow more slowly. In lung cancer models with a KRAS mutation, suppressing the enzyme also helped restore the tumors' sensitivity to the drug sotorasib and increased the animals' survival.

Patient data and limitations

An analysis of patient data showed that high METTL13 activity in tumors is associated with a worse response to drugs targeting KRAS. This links the laboratory mechanism to the clinical picture: the enzyme's level may indicate the likelihood of responding to therapy. The authors believe that targeting METTL13 could become a way to fight tumors, including those resistant to existing treatment, but they emphasize that before such an approach can be applied in humans, a safe way to target the enzyme must be developed and its effectiveness tested in clinical trials. Thus, for now this concerns preclinical results and a potential direction, not a ready-made treatment method.