January 22, 2003
Joint study on protein-cancer connection underscores promise of targeted therapies
Jonathan Fletcher, MD
Researchers at Brigham and Women's Hospital (BWH), Dana-Farber, and Oregon Health and Science University have discovered that a defective protein may be responsible for some cases of gastrointestinal cancer.
The study, published in the Jan. 9 issue of the journal Science, involved a rare form of digestive-tract cancer known as gastrointestinal stromal tumor (GIST). Previous research had shown that many cases of this disease result from a faulty enzyme called KIT. It was not clear what lay behind the remainder of gastrointestinal stromal tumors.
In the new study, scientists found that a particular protein was defective in about 35 percent of GIST cases where the KIT enzyme was normal. The finding may lead to new therapies because drugs known as small molecule inhibitors are able to counteract flawed versions of the protein, called PDGFRA. (One well-known small molecule inhibitor is Gleevec, which works by blocking the action of the defective KIT enzyme.)
George Demetri, MD
"This discovery lends further credibility to the idea that many kinds of cancer cells can be targeted by selective therapies, as opposed to conventional chemotherapy that destroys even healthy cells," said the study's senior author, Jonathan Fletcher, MD, of BWH and Dana-Farber. "While these drugs might not cure the cancer, they do give us one more treatment option, and fortify the hope that other kinds of cancer can be treated this way."
Besides Fletcher, contributors included Michael Heinrich, MD, of Oregon Health and Sciences University, Christopher Fletcher, MD, of BWH and Dana-Farber, and George Demetri, MD, director of Dana-Farber's sarcoma program.
According to Fletcher, the study does more than point scientists toward potential new therapies for gastrointestinal stromal tumors. By demonstrating that two mutant proteins can be independently responsible for GIST, the findings suggest that multiple mutations may underlie other types of cancer as well.
"Certainly these findings leave us wanting to test other proteins for their potential roles in cancer development," Jonathan Fletcher remarked. "Such precision-targeting of cancer cells holds enormous promise."
(This story first appeared in the Jan. 22, 2003, edition of Inside the Institute.)
