Small Study Identifies Eight Genes that Predict Response in Metastatic Melanoma

Melanoma is on the rise, and metastases can develop virtually anywhere, with the brain and kidneys as common sites. Hussein Tawbi, MD, MSc, assistant professor of medicine, University of Pittsburgh School of Medicine, said, “Only 7 to 10% of patients are likely to respond to the current standard of care.” Dr. Tawbi and colleagues decided to look for biomarkers that might predict response to alkylator-based chemotherapy used to treat metastatic melanoma. They identified eight genes that they believe may form a profile useful in distinguishing responders from nonresponders.

The investigators looked at tissue samples from 21 patients who had been treated for malignant melanoma with the standard chemotherapy regimen of temozolomide (Temodar) and dacarbazine. Patients were stratified according to response and nonresponse. Then the researchers used neural network analysis to survey the patients’ genes and their regulators for differences between the two groups. “neural network analysis,” said Dr. Tawbi, “helped us identify a signature of 8 genes and their switches that predict a patient’s likelihood of responding to treatment for metastatic melanoma.” Dr. Tawbi suggested that the eight-gene profile might be potential therapeutic targets. Few treatment options exist for patients with metastatic melanoma, and for the 90% who do not respond to chemotherapy, the survival outlook is extremely poor.

The results of the study are limited by the small sample size. Researchers are attempting to validate the results in a trial of 80 patients.