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FEATURE ARTICLE

Fighting Cancer Through the Study of Sarcomas

Although rare, cancers of the muscle, bone or fat carry the same molecular errors as other tumors, making them ideal subjects for the discovery of new therapies

Igor Matushansky, Robert Maki

A 50-year-old Finnish woman was having mild stomach pains when she went to see her doctor in 1996. The physician in Helsinki found a large abdominal mass, and things got worse from there. Further exams discovered tumors, 7 and 10 centimeters in diameter, on her stomach, plus many small nodules of spreading cancer. Surgeons removed as much of it as they could find, but the diagnosis was grim. It was a gastrointestinal stromal tumor, or GIST, a cancer of the connective tissue in the gut that was inevitably fatal if surgery failed.

Figure 1. From a distance, cancer looks like a single disease...Click to Enlarge Image

Two years later the cancer was back, and doctors had to operate again to remove growths on the liver and abdominal wall. Another surgery that year excised more tumors on the liver and ovary. The woman's doctors tried to slow the proliferating cells with an intense barrage of combined chemotherapeutics—seven cycles using four different drugs over a five-month period—without success. As the cancer spread, it blocked the patient's intestine, requiring yet another operation. When the surgeon went in to cut away the blockage, he found and removed 45 additional tumors. The patient began taking large daily doses of two cutting-edge, immune-system-enhancing drugs, to little effect.

Having exhausted other options, the woman's oncologist, Heikki Joensuu at the Helsinki University Central Hospital, suggested an experimental drug, STI571, which had just begun phase I testing for chronic myelogenous leukemia—a completely different kind of cancer from the soft-tissue tumors his patient carried. It was a desperate attempt to save the patient's life, so despite the lack of any clinical supporting data, the hospital agreed to let him try.

Two weeks later, an MRI exam showed the woman's tumors were 40 percent smaller. Two months later, they had shrunk half as much again. At eight months, they were further reduced in size; about a quarter were no longer detectable. What's more, the tumor cells that remained had stopped dividing and no longer showed the molecular signature of cancer. It was an incredible improvement.

Why did Joensuu think to try this particular drug? Because he knew, based on the work of others, the molecular basis of GIST: The abnormal protein that caused his patient's tumor was similar to the one that caused the leukemia for which the drug was approved. Furthermore, some reports indicated that STI571 could work on both types of proteins—at least in a dish of cultured cells. In the end, this success owed much to many: The paper describing this striking case included as coauthors doctors and scientists from Helsinki, Turku University (also in Finland), Massachusetts Institute of Technology, Harvard, the Oregon Health Sciences University and the pharmaceutical company Novartis, which made the compound (now called imatinib and sold under the name Gleevec).

Is this drug the long-sought silver bullet, the cure for all types of cancer? No. But it does illustrate how discoveries in research labs can quickly pay off in clinics. It is an early fruit from what promises to be a great harvest of medical advances made possible by two decades of accelerating progress in understanding how cells work. And it can't come soon enough.





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