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Scientists have isolated a group of genetic mutations involved in the growth of melanoma, the deadliest form of skin cancer. Their work may lead to therapies with existing drugs that target the same mutations.
Led by Yardena Samuels of the National Human Genome Research Institute, the research team from the U.S. National Institutes of Health (NIH) sequenced the protein tyrosine kinase (PTK) gene family in tumor and blood samples from people with metastatic melanoma. Their study is published in the September issue of the journal Nature Genetics.
"We have found what appears to be an Achilles' heel of a sizable share of melanomas," Samuels, an investigator in the cancer genetics branch of the institute's Division of Intramural Research, said in a NIH news release.
The PTK family includes many genes that, when mutated, promote many types of cancer, including brain, gastric and lung malignancies, according to background information provided in the news release. In the new NIH study, one PTK gene that appeared particularly suspicious was the ERBB4 gene. Scientists found ERBB4 mutations in 19% of patients' tumors, making it the most frequently mutated PTK gene in melanoma. Additional lab studies found that melanoma cells with the ERBB4 defect were dependent on the mutant gene for their growth. The researchers also found that two additional PTK genes—FLT1 and PTK2B—were mutated in about 10% of the tumor samples.
The discoveries could open up new avenues for therapies. For example, the researchers discovered that melanoma cells grew much more slowly when exposed to lapatinib (Tykerb), a chemotherapy drug that inhibits ERBB4. Lapatinib is already in use by some breast cancer patients. The NIH team is planning a clinical trial using lapatinib in patients with metastatic melanoma harboring ERBB4 mutations.