In his first few weeks as head of the melanoma group at Memorial Sloan-Kettering Cancer Center seven years ago, a young man walked into Dr. Gary Schwartz's office with a rare form of the skin cancer that affects the eye. "It was horrible. He died of metastatic disease. He was only 24. I promised him I would find a way to cure his cancer," recalls the physician-scientist of the patient who helped inspire his quest to find an effective treatment for uveal melanoma, which affects 2,000 to 3,000 patients each year. Researchers from Memorial-Sloan Kettering on Saturday reported results of the first clinical trial ever to show that a drug helped patients with advanced uveal melanoma at the American Society of Clinical Oncology Meeting in Chicago. The mid-stage clinical trial led by Dr. Richard Carvajal, Schwartz's colleague, found that an experimental drug from AstraZeneca called selumetinib shrank tumors in half of all treated patients and doubled progression-free survival, a measurement of the amount of time a medicine controls cancer before it starts to grow again. "This represents the first real victory in medical oncology for patients with uveal melanoma," said Schwartz, who is chief of the New York hospital's melanoma and sarcoma service. Melanoma of the eye is far different from other forms of the deadly skin cancer, and attempts to treat it in the past have largely failed. Out of a total of 157 patients treated in eight different prior clinical trials, only two patients had significant tumor shrinkage. Like skin melanoma, uveal melanoma is caused by specialized, pigment cells called melanocytes, but biologically it is "completely distinct from skin melanoma," Carvajal said in a telephone interview. "Nothing has ever been shown to help patients with metastatic uveal melanoma before," he said. Most patients are diagnosed with early stage disease, and treatments range from radiation and surgery to remove the tumor to full removal of the eye. In spite of these efforts, the disease spreads to other organs in about half of patients, giving them an expected survival of nine to 12 months. About 90 percent of patients with this cancer have mutations in genes called Gnaq and Gna11. Through work in Schwartz's lab, researchers discovered that these mutations trigger a known cancer pathway called MAP kinase that helps feed the cancer. Schwartz and Carvajal began looking for ways to shut down this growth driver using drugs under development that block different aspects of this pathway. Selumetinib, which blocks a protein called MEK, appeared to work. "We showed if you take a cell with the mutation and drop this drug in there, you can actually prevent the cell from growing," Schwartz said. (For more Life & Style news and updates, follow us on Twitter:@AhramLifestyle) http://english.ahram.org.eg/News/72913.aspx
