The research suggested that PTHrP alone doesn't directly cause muscle wasting, yet blocking the protein's activity prevents it.
Thus, the role of PTHrP "is definitely not the whole answer" to the riddle of cachexia, noted Spiegelman, but may be a necessary part, while other factors are also involved.
A collaborator on the study, Vickie E. Baracos, PhD, at the University of Alberta in Edmonton, Canada, provided the blood of 47 patients with lung or colon cancer who were cachexic. Serkan Kir, PhD, from the Spiegelman lab and first author on the paper found increased levels of PTHrP in 17 of the patients. Those patients had significantly lower lean body mass and were producing more heat energy at rest than were the other patients in the group.
It may turn out that the PTHrP mechanism is responsible for cachexia in a subset, but not all, cancer patients, Spiegelman suggested. Before trying the anti-PTHrP antibody in human patients, he said, "clinicians would probably first want to find out if the protein is elevated in certain cancers, and determine which patients would be good candidates for a clinical trial."
Barrett Rollins, MD, PhD, Dana-Farber's chief scientific officer, commented that the report from Spiegelman and his colleagues "provides a new roadmap for developing a rational, mechanistically based treatment for this incredibly debilitating condition that occurs in such a large number of our patients. Until now we've had no truly effective way to reverse this horrible complication."
Patients with upper gastrointestinal and pancreatic cancers are the most likely to develop cachexia, and the condition affects about 80 percent of terminal cancer patients. Current strategy is to give appetite stimulants and nutrient supplements, along with medications to counteract some of the molecular pathways believed to underlie the wasting process, but with
|Contact: Teresa Herbert|
Dana-Farber Cancer Institute