Attacking sarcoma from all sides
By Robert Levy
Positron emission tomography (PET) technology is helping Annick Van den Abbeele, MD, and others see whether new patient therapies are working.
Annick Van den Abbeele, MD, director of Dana-Farber's Division of Nuclear Medicine, could barely believe the image on the screen of the Institute's positron emission tomography (PET) scanner. The machine, which shows tumors as dark blobs within the ghostly outlines of a human figure, was displaying scan results from a 40-year-old woman with a rare digestive tract cancer called gastrointestinal stromal tumor (GIST).
When the patient had been scanned a month earlier, the PET device depicted an enormous mass in her abdomen. Now, after just a few weeks on a new investigational drug, there was no sign of the tumor; Van den Abbeele could see only an empty space where the mass had been.
"I thought this was an image of the wrong patient," recalls Van den Abbeele, clinical director of the joint Department of Radiology of Dana-Farber and Brigham and Women's Hospital (BWH). "I'd never seen a response like that in sarcoma," the family of connective tissue cancers that includes gist.
Later that afternoon came a déjà vu. A patient receiving the same therapy—and who a month earlier had a gist the size of a grapefruit in his liver—came in for a scan. His tumor had also disappeared. "I picked up the phone and told George Demetri [MD, director of Dana-Farber's Sarcoma Program], 'You need to see this, something is working.'"
The patients were the first in the United States to participate in the pivotal clinical study of the drug Gleevec for gist. By the time the trial was completed a year later, it was clear that Gleevec, originally developed for patients with a chronic form of leukemia, was the first drug ever shown to be effective against gist.
This story from 2000 exemplifies what Dana-Farber and its main partners in sarcoma research—Brigham and Women's, Children's Hospital Boston, and Massachusetts General Hospital—do best. It was DFCI and BWH researchers who helped prove that gist is a distinct form of sarcoma. It was investigators at the same institutions who reasoned that a single genetic flaw in gist cells caused the cancer and might make them vulnerable to Gleevec. It was a team of Dana-Farber researchers who conducted the clinical trials to prove Gleevec's effectiveness. And it's the same team that has now shown the usefulness of a secondgeneration drug, called sunitinib, soon to be known as Sutent, for patients whose disease relapses after treatment with Gleevec.
"Our work with biotechnology and pharmaceutical firms is changing the model by which sarcoma therapies are developed."
—George Demetri, MD
"Our track record is a reflection of the fact that we talk to one another," Demetri says, playfully understating a spirit of cross-specialty collaboration that is rare in sarcoma research. "We've brought together people from a variety of disciplines—molecular research, pathology, clinical research, imaging, specialized nursing, and social work—so we can quickly develop ideas that result in new diagnostic and therapeutic approaches. It's a matter of mutual trust, and it's why we have more novel drugs in development to target sarcomas than anywhere else on the planet."
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