A Triumph in the War Against Cancer

Oncologist Brian Druker developed a new treatment for a deadly cancer, leading to a breakthrough that has transformed medicine

"We're just seeing the start of matching patients with the right drug and seeing rapid improvements," says Dr. Brian Druker. (Robbie McClaran)
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“He lets the science do the talking.”

Druker grew up the youngest of four children in St. Paul, Minnesota, and attended public schools, excelling at math and science. His father was a chemist at 3M whose work on printing processes was patented. His mother was a homemaker who got involved in school-board politics and ran unsuccessfully for the state legislature. After graduating with a chemistry degree from UC San Diego, he stayed on, and in 1978, his first year in medical school, he wrote a 16-page paper hinting at a future he would help create. Written in longhand with blue ink on lined notebook paper and titled “Cancer Chemotherapy,” it concluded that, someday, when the action of cancer drugs is “understood in biochemical terms the field of cancer chemotherapy should make advancements far beyond the progress already made.”

After the Dana-Farber Cancer Institute gave him the bum’s rush, Druker marshaled new resolve. “When I moved here to Oregon, my goal was to identify a drug company that had a drug for CML and get that into the clinic,” he said.

He’d previously met Nick Lydon, a biochemist at the Swiss pharmaceutical firm Ciba-Geigy (which would merge with Sandoz in 1996 to form Novartis). Lydon had collaborated with Roberts, Druker’s former lab chief. “I called my friend Nick at Ciba-Geigy and he said, ‘We have what you’re looking for.’” It was called STI571. Company chemists had synthesized it and other compounds while searching for a new anti-inflammatory drug, but they had learned it could also block the activity of enzymes in a test tube. Still, they hadn’t quite decided what to do with the compound.

In August 1993, Druker received his first batch of liquid STI571 and another candidate compound from Switzerland. Using the enzyme-measuring tool he’d helped develop, he confirmed that STI571 strongly inhibited the BCR-ABL enzyme, which belongs to a class of enzymes known as tyrosine kinases; the other compound did so only weakly. He also poured minute amounts of STI571 into a tray of thimble-size containers that held fluid and live white blood cells derived from a CML patient. Druker had hoped the cells’ growth would slow or stop. Even better, the cells died. Moreover, a large amount of STI571 given to healthy cells in a dish did no harm. “Brian’s contribution was critical,” Lydon recalled, in convincing the company to “move in that direction.”

But, of course, the road to dashed hopes is paved with experimental drugs that looked terrific in a test tube but failed in human beings. Skeptics pointed out that hundreds of different types of tyrosine kinase enzymes are at work in the body, and, they added, wouldn’t a drug that blocked one also block many others and wreak physiological havoc? “There were many naysayers who argued that it would be impossible to develop specific protein kinase inhibitors” for treating cancer, Tony Hunter, a biochemist at the Salk Institute in La Jolla, California, wrote in the Journal of Clinical Investigation.

Scientific ideas don’t take root like dandelion seeds wafted onto fertile ground. They need advocates, people who want to win. Druker plugged away, doing more experiments, such as inducing a form of CML in laboratory mice and subjecting them to STI571. It all but eliminated the animals’ disease. “I was putting in probably 60 to 80 hours a week,” recalled Druker, who in his scant free time competed in bicycle races, a sport that demands a high tolerance for pain and a sense of when to break out of the pack. “My life in those days was I’d work [in the lab], work out, eat and sleep.” What was driving him, he said, were CML patients who were dying.

By 1997, having published numerous studies with co-workers in Portland and Switzerland, Druker believed the compound was ready to be tried in human beings. Novartis disagreed. For one thing, when dogs had been given the drug in intravenous form, it tended to cause blood clots at the end of the catheter. Novartis chemists spent months reformulating the liquid drug as a pill. But when the researchers gave large doses to dogs, the animals showed signs of liver damage. Some company officials, Druker recalled, advised dropping the project altogether.

But the canine liver damage didn’t faze him; chemotherapy, after all, is destructive. “We knew how to give people toxic cancer drugs,” he said.

The next thing Druker did may not have been illegal, but it certainly wasn’t kosher. He bypassed Novartis and went straight to the Food and Drug Administration to see if he’d accumulated enough data to start a human trial. “I called up the toxicologist at the FDA and said, ‘Here’s the problem.’ And he said, ‘My goodness, you have a ton of data, we would probably accept this application.’” Druker then told Novartis what he’d done. “I got myself in some hot water because I’d gone behind their back.”


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