New skin cancer suppressor gene discovered

Researchers at the National Institutes of Health (NIH) have identified a gene that may suppress the growth of malignant melanoma, the deadliest type of skin cancer. Their findings, published in the journal Nature Genetics, follow a systematic genetic analysis of a group of enzymes associated with skin and other cancers.

The NIH study found that one-quarter of melanomas have alterations (or mutations) in the genes that encode matrix metalloproteinase (MMP) enzymes. MMPs and other important enzymes play a functional role in tumor growth and disease spread, paving the way for more personalized cancer treatments.

Members of the MMP gene family are often considered oncogenes, and many tumors express high levels of MMP enzymes, and researchers have spent decades pursuing MMPs as promising targets for cancer therapy. However, when MMP inhibitors were tested in patients with a variety of cancers, the drugs failed to slow tumor growth and sometimes even accelerated it.

The latest research may help explain why drugs designed to treat melanoma by blocking MMP enzymes have performed so poorly. Because it turns out that the MMP gene that is most commonly mutated in melanoma is not an oncogene at all. Researchers at the National Human Genome Research Institute (NHGRI) found that MMP-8 actually acts as a cancer suppressor gene in melanoma. About 6% of melanoma patients have tumors that contain mutated MMP-8 genes or related tumor suppressor genes, so blocking all MMP genes is not a wise treatment. The study suggests that a better treatment approach would be to find drugs to restore or increase MMP-8 function, or to block only those MMPs that are true oncogenes.