Scientists at The University of Texas MD Anderson Cancer Center have found that the enzyme METTL13 helps cancer cells produce proteins needed for tumor growth more rapidly. These include KRAS, which plays an important role in the development of many types of cancer. The findings were published in the journal Nature Cell Biology.
The discovery centers on the enzyme METTL13. The researchers found that it adds a chemical tag to one of the proteins involved in producing other proteins inside cells. This modification helps the cellular machinery read genetic instructions more efficiently and produce larger amounts of certain proteins, including KRAS, which drives the growth of many tumors.
"The KRAS gene is frequently mutated in lung and pancreatic cancers. Although drugs that block its activity have become available, tumors sometimes adapt to treatment and develop resistance to these medications," the scientists explained.
In experiments using preclinical models, reducing METTL13 activity decreased the production of KRAS and other proteins that support cancer cell growth. As a result, tumors grew more slowly. In KRAS-mutant lung cancer models, suppressing the enzyme also helped restore tumor sensitivity to the drug sotorasib and increased animal survival.
In addition, an analysis of patient data showed that high METTL13 activity in tumors was associated with a poorer response to drugs targeting KRAS.
The researchers believe that targeting METTL13 could offer a new approach to fighting tumors, including those resistant to existing treatments. However, before this strategy can be used in humans, a safe way to target the enzyme must be developed and its effectiveness evaluated in clinical trials.
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