NEW YORK, FEBRUARY 13, 2013 The experimental drug selumetinib may allow some patients with advanced thyroid cancer to overcome resistance to radioiodine (RAI), the most effective therapy for the disease, according to new research from Memorial Sloan-Kettering Cancer Center.
Published in the February 14 issue of the New England Journal of Medicine, the study offers new hope for patients with a disease that can have a poor prognosis. An estimated 56,000 new cases of thyroid cancer are diagnosed each year in the United States, and that number is on the rise, according to the National Cancer Institute. About 5 percent of these patients will eventually develop distant metastatic disease, and the ten-year survival rate for patients with metastatic tumors that fail to respond to RAI is approximately 10 percent.
According to James A. Fagin, MD, Memorial Sloan-Kettering's Endocrinology Service Chief and senior author on the study, many trials have tested strategies for overcoming RAI resistance in metastatic thyroid cancers, but none have been successful. Previous studies have shown that a cell's ability to absorb RAI is controlled by the MAPK pathway, so Dr. Fagin and his colleagues examined whether selumetinib, an MAPK inhibitor, could reverse RAI resistance by inhibiting the signaling of genetic mutations in this pathway. The approach proved effective, especially in patients with thyroid cancers that contain a mutation in the RAS gene a component of the MAPK pathway.
"Blocking this key pathway increased the uptake of iodine, making radioiodine treatment potentially effective once again," said Fagin, who led this research in cells and in mice.
Following a five-day low-iodine diet, researchers administered selumetinib to 20 patients with tumors resistant to radioiodine. After four weeks, patients underwent a diagnostic scan that measured how much RAI their tumors would absorb. In eight patients, including all five with an
|Contact: Caitlin Hool|
Memorial Sloan-Kettering Cancer Center