folkman and angiogenesis (zt)

Moses Judah Folkman 1933-2008

By ANDREW POLLACK

Published: January 16, 2008

Dr. Judah Folkman, a path-breaking cancer researcher who faced years of skepticism before his ideas led to successful treatments, died Monday in Denver. He was 74.


The cause was apparently a heart attack, his wife, Paula Folkman, said Tuesday. Dr. Folkman died at the airport, where he was changing planes on the way to a conference in Vancouver, British Columbia.

Dr. Folkman, a professor at Harvard and director of the vascular biology program at Children’s Hospital Boston, is considered the father of the idea that tumors can be kept in check by choking off the supply of blood they need to grow.

The approach is now embodied in several successful cancer drugs, most notably Avastin, by Genentech.

“His vision and ideas literally changed the course of modern medicine,” said Dr. William Li, a former student of Dr. Folkman’s, who is president of the Angiogenesis Foundation, an organization that promotes the promise of Dr. Folkman’s approach. Angiogenesis refers to the formation of new blood vessels.

Dr. Folkman’s work created a frenzy in 1998 when a front-page article in The New York Times reported how two drugs he had developed had eradicated tumors in mice. The article quoted Dr. James Watson, a Nobel laureate for discovery of the structure of DNA, as saying, “Judah is going to cure cancer in two years.”

But some other scientists had trouble replicating Dr. Folkman’s results, and the biotechnology company with rights to the drugs gave up on them to save money after the drugs did not seem to work as well in people as in mice.

While an improved version of one of those drugs eventually won approval in China, the drugs on the American market that work by blocking tumor blood supply were developed by others, not by Dr. Folkman. But experts say those drugs might not exist but for Dr. Folkman’s work.

“The controversies are minor,” said Dr. David G. Nathan, president emeritus of the Dana-Farber Cancer Institute in Boston and a longtime colleague of Dr. Folkman’s. “The point is, he made the field.”

Moses Judah Folkman was born in Cleveland on Feb. 24, 1933, the son of a rabbi, and was raised in various places in the Midwest. He often told of how when he was about 7 he would sometimes accompany his father on visits to hospital patients.

The excitement of those visits one day emboldened young Judah to tell his father that he wanted to be a doctor instead of a rabbi. “So,” his father replied, “you can be a rabbi-like doctor.”

Many of his colleagues say that the charismatic Dr. Folkman achieved that, with legions of devoted students and patients.

“He had a list of patients who wanted information from him,” said Robert Cooke, the author of “Dr. Folkman’s War: Angiogenesis and the Struggle to Defeat Cancer.”

“Even when he was out of town,” Mr. Cooke said, “he called 10 a night.”

Dr. Folkman attended Ohio State University and then Harvard Medical School. Trained as a surgeon, he was chosen to be surgeon in chief at Children’s Hospital Boston in 1967, when he was 34. But he devoted much of his time to research.

While working for the Navy in 1960 on blood substitutes, Dr. Folkman began experimenting with tumors and found that all grew to the same size. He hypothesized that the tumors could not grow beyond a certain size without a blood supply and that tumors must have some mechanism to induce the formation of blood vessels. He published his research in 1971.

At first, Dr. Folkman was largely ignored by other researchers who focused on directly killing cancer cells.

But Dr. Folkman persisted and his ideas gradually gained support. A crucial moment came in the late 1980s when a scientist at the biotechnology company Genentech reported the discovery of vascular endothelial growth factor, a protein that spurs the formation of new blood vessels.

The company’s drug, Avastin, developed to block that protein, was approved for use in 2004.

Avastin and Lucentis, another Genentech drug, have also had great success in restoring vision to people with eye diseases characterized by leaky blood vessels in the back of the eye.

Still, even now there is some controversy. Rakesh Jain, professor of tumor biology at Harvard Medical School, maintains, for instance, that Avastin and the other drugs actually do not work by choking off the flow of blood to the tumor. Rather, he said, they help fix the leaky, twisty blood vessels that feed tumors, thereby improving the delivery of cancer-killing chemotherapy drugs.