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The Anti-Cancer Strategist


One could excuse Dr. Judah Folkman if he decided to kick back. The 72-year-old cancer specialist is often called the father of anti-angiogenesis, the scientific term for blocking the growth of new blood vessels. He theorized in the early 1960s that the technique might be used to starve tumors to death -- then spent decades trying to win over a skeptical medical establishment. Today, the most successful of the new targeted cancer drugs, Avastin, uses this tactic, as does a promising vision loss treatment, Lucentis. Both drugs are from Genentech Inc. (DNA). In total, more than 30 such treatments are in human trials.

As director of the Vascular Biology Program at Children's Hospital in Boston and a professor at Harvard Medical School, Folkman continues to treat patients and train young doctors. But his latest passion is the hunt for "biomarkers" -- proteins found in blood, saliva, or urine that signal the presence of disease. If biomarkers could be found for the hundreds of different types of cancers, doctors could treat each patient only with the drugs that are most likely to work.

It has proven extremely hard to identify these tumor "fingerprints," however. There may be 20,000 different proteins circulating in the blood, but few tests link any one of them decisively to a cancer. As a result, targeted cancer therapies are given to a broad swath of patients, even though the drugs rarely work for more than 25% of them.

Folkman's lab is trying to improve that ratio by screening for biomarkers associated with tumor angiogenesis. He envisions a day in the not-so-distant future when cancer drugs will be prescribed based on biomarkers matched to tumors, much as antibiotics are matched to specific microbes. "Ideally, we will never treat the tumor. We will treat the biomarker," says Folkman.

He is already testing that idea. One of Folkman's patients is a 20-year-old man who had a rare thyroid tumor removed when he was 13. To detect potentially deadly recurrences, doctors then monitored a known biomarker, a calcium-controlling hormone called calcitonin, in the boy's blood. When levels started rising four years ago, the boy's physician father knew the cancer would inevitably return. Rather than wait, he asked Folkman to treat the rising calcitonin levels. In mid-May the patient started receiving doxycycline, an antibiotic that also blocks blood vessel growth.

Folkman's desire to help patients was kindled at age 7 as he accompanied his rabbi father on hospital visits. After graduating from medical school in 1957, he worked for the U.S. Navy, where he co-developed the first implantable devices for the sustained release of drugs. In a Navy lab, he also observed something odd: Tumors that grew perfectly well in mice would stall out in cell cultures, where they no longer had access to blood vessels. Other scientists had done research on angiogenesis, but it was Folkman's groundbreaking 1971 paper linking it with cancer that ignited the field. Two decades later his lab discovered two compounds, endostatin and angiostatin, that shrank tumors in mice. In 1998 media reports trumpeted these early results as cancer cures -- leading to bitter disappointment when endostatin proved hard to make. But with the success of Avastin and other new drugs, Folkman has been vindicated.

Back working with mice, Folkman's lab has found several potential biomarkers that appear like clockwork 20 to 40 days after tumor angiogenesis switches on. "This is pretty exciting stuff," he says. Clearly not a man ready for retirement.

By Catherine Arnst


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