Discoveries
Designer drug may succeed as frontline treatment for chronic myelogenous leukemia, study shows
After Gleevec® was introduced in 1998, it rapidly became the frontline treatment for chronic myelogenous leukemia (CML). However, although 95 percent of patients initially respond to Gleevec, between 25 and 50 percent of those with advanced forms of CML — and 4 percent of those with early forms — relapse each year.
Now researchers at Dana-Farber have tested a "next generation" drug discovered and developed by Novartis Pharma AG that in animal studies is 20 times more potent than Gleevec, opening the way for the first trials of the drugs in humans. Called AMN107, the drug was designed to fit more snugly than Gleevec into a tiny "pocket" on the surface of CML cells, thereby turning off the cells' growth machinery.
In experiments with laboratory samples of CML cells, AMN107 killed leukemic cells more effectively than Gleevec. In follow-up studies with mice with a human form of this leukemia, AMN107 produced lengthier remissions than Gleevec and triggered remissions in rodents in which the disease had become resistant to Gleevec. Side effects in the mice were minimal.
"We're very encouraged by the results so far," says the study's senior author, James Griffin, MD, chair of DFCI's Department of Medical Oncology. "This is an elegant example of how rational drug design—developing drugs based on a molecular understanding of cell structures and processes—can be used to attack human diseases."
