Gleevec: The Dana-Farber Connection
By Richard Saltus
George Demetri, MD, led an effort to try a new leukemia drug, Gleevec, against
a rare, but lethal GIST cancer (gastrointestinal stromal tumor). Here, Demetri points to scans showing that a large tumor (orange blob in scan above, left) disappeared (below, left) after Gleevec treatment. George Demetri, MD, led an effort to try a new leukemia drug, Gleevec, against a rare, but lethal GIST cancer (gastrointestinal stromal tumor). Here, Demetri points to scans showing that a large tumor (orange blob in scan above, left) disappeared (below, left) after Gleevec treatment.
Harvard University Gazette photo by Jon Chase
Told she had only a year or so to live, Phyllis Carter flew from her Florida home to Boston last year, hoping that doctors at Dana-Farber Cancer Institute could offer something — anything — to improve her odds.
Pains in her side had been traced to a baseball-sized tumor in her stomach, a rare cancer called GIST. More tumors had sprouted in her liver, and her Florida doctors projected that she had "one to three years, even if I took chemotherapy, because the chemo would fail," says Carter, 64, who has four children and six grandchildren. The news that GIST (gastrointestinal stromal tumor) was invariably fatal, she said, "just devastated me."
The timing of her trip to Boston in October 2000 was fortunate. Not often do cancer specialists have a promising new treatment to offer desperately sickpatients. But a novel drug called STI-571, known commercially as Gleevec, had become the talk of the cancer world in 1998 and 1999 when patients with the life-threatening cancer CML (chronic myelogenous leukemia) responded dramatically in its first tests.
Dana-Farber's George Demetri, MD, was studying the effects of Gleevec in patients with GIST, the cancer affecting Carter. By the time she came to Boston, unprecedented results had been achieved. In the majority of patients, the stubborn GIST tumors had stopped growing or even shrunk.
When Carter arrived at DFCI, Demetri put her on a regimen of six orange Gleevec capsules a day. Unlike most chemotherapy drugs, Gleevec can be taken by mouth at home, and it has few serious side effects. Within six weeks, scans showed her stomach tumor had been reduced by 60 percent, and the liver tumors were also fading.
Another GIST patient in a desperate state, Sandra Merriman of Minneapolis, came to Dana-Farber in July 2000 when six operations to remove tumors had failed to halt the rapidly spreading disease. A few weeks after she began taking Gleevec, the tumors started shrinking; by the following March, their total bulk had decreased by 73 percent.
Gleevec has been called the first "smart" cancer drug because it's designed to disable cancer cells with a precise attack, leaving normal cells uninjured. It was discovered by scientists at Novartis Pharmaceuticals, who relied on key findings, molecular tools, and advice from Dana-Farber researchers to support their efforts.
These new drugs can be compared to precision-guided weapons, designed as alternatives to punishing chemotherapy drugs that poison tumors, but also harm normal tissue.
"We helped set the stage for the drugs that came out of that project [from the drug company]," says Thomas Roberts, PhD, of the Institute's Cancer Biology Department, who, with fellow researcher Charles Stiles, PhD, was an advisor to the Novartis drug discovery program. Some of Stiles' research on chemical signals that prompt cell growth helped define targets for the first smart drugs designed to attack cancer with pinpoint accuracy.
Gleevec is no panacea: it's been shown to work only in two types of cancer thus far, CML and GIST. But scientists say it shows how effective new drugs can be that are designed to attack weak points in cancer cells without harming normal cells and tissues. Drugs like Gleevec squelch abnormal chemical signals inside cells, or on their surface, that have enabled the cell to escape normal controls and grow wildly and dangerously.
Combating many forms of cancer will probably require a variety of targeted drugs used in combination, as cancer involves different types of malfunctioning genes and no one or two drugs will be sufficient. Some cancers — particularly more common tumors of the breast, lung, and prostate — may be harder to treat because they are caused by multiple signaling pathways running amok, rather than just one, as in CML and GIST.
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