2/19/01 Newsweek article about Judah Folkman / angiogenesis, etc.
Folkman Looks Ahead.
The controversial pioneer of angiogenesis is back on the
map—and now his theories are being tested on humans.
By Claudia Kalb
NEWSWEEK
Feb. 19 issue — On the 10th floor of Boston’s Children’s
Hospital, Dr. Judah Folkman—a gentle presence with a
racing mind—sits down to talk. He offers coffee and
cookies. He teaches, he questions, he wonders.HE PLUNGES BACK to the past, hurtles ahead to the
future and then, bounding through his lab in his scientist’s
white coat, he marvels at the present. “Look at this,” he says,
peering at a cylinder filled with sloshing red liquid. “These are
human tumor cells.” Tiny white dots, like grains of sand—they
are the vicious beasts that Folkman, 68, has spent a lifetime
trying to tame. And not, he insists, without the help of others.
Walking past lab tables cluttered with flasks and tubes, he
greets his collaborators, boasting about their discoveries. “I’m
conducting an orchestra here,” he says. “I’m listening to the
music.”
And the tempo is picking up. Angiogenesis, Folkman’s
once derided theory that tumors grow by recruiting blood
vessels for nourishment, is now widely accepted as a
promising avenue in cancer treatment—and it is finally moving
from experiments in mice to testing in humans. At least 20
drugs called angiogenesis inhibitors are now in clinical trials,
including angiostatin and endostatin, the compounds isolated by
Dr. Michael O’Reilly in Folkman’s lab. Today, three years after
those molecules were trumpeted on the front page of The New
York Times—igniting first a media frenzy amid hopes for a
cancer cure and then a backlash casting doubt on his
results—the spotlight is once again on Folkman. A new book,
“Dr. Folkman’s War,” is just hitting stores and, later this
month, public television’s “Nova” will air “Cancer Warrior,”
chronicling Folkman’s pioneering work in the field.
WAITING FOR ANSWERS
The scientific community, meanwhile, is watching for
data. The angiostatin trials, taking place at Thomas Jefferson
University Hospital in Philadelphia, are still getting underway.
But endostatin, under study at the Dana-Farber Cancer Institute
in Boston, the M.D. Anderson in Houston and the University of
Wisconsin in Madison, is already showing precisely what
scientists had hoped for in phase-one safety testing: while it is
far too soon to judge its effectiveness against cancer, it causes
virtually no side effects. Although patients in these early trials
are exceedingly sick and most saw their cancer continue to
grow, there were some very preliminary positive signs: tumors
stabilized or even regressed partially in several patients. And
sophisticated imaging showed that as doses of endostatin
increased, blood flow to tumors decreased in some
patients—the goal of angiogenesis inhibitors. There is still
healthy skepticism about whether one drug alone can shut
down blood-vessel growth. And there is plenty to learn as trials
continue. What is an effective dose? When in treatment should
endostatin be given? Will a 24-hour continuous infusion of the
drug, now being tested in patients, improve response and
survival? “I think proof of concept is there,” says M.D.
Anderson’s Dr. Roy Herbst, “but we still need to do a lot of
work to eke out exactly how to use them.”
Even people like Duane Gay, one of the first humans to
be treated with endostatin, knows that the drug may not save
him. Three years ago, on his first wedding anniversary, Gay,
44, learned that the connective-tissue cancer he’d kept at bay
since 1991 had come roaring back. Endostatin, which he was
given after traditional therapies failed, didn’t eradicate the
disease: a tumor in his rib grew by more than half. But masses
in his liver, lungs and kidney stabilized, giving him hope—and
boundless enthusiasm for the potential of anti-angiogenesis
therapy. “I went in hoping that it would save my life, but I also
feel privileged that I could help advance the science.” Now,
Gay and his wife are “praying for the scientists,” he says. “And
at the top of the list is Dr. Judah Folkman.”
Folkman, the son of a rabbi—who told him on his bar
mitzvah day, “Be a credit to your people”—is committed to
answering those prayers. It hasn’t been easy. He battled
skeptics decades ago and he’s battled them since by simply
plowing ahead with his research. Today, as scientists and
biotech companies pour time and money into developing
angiogenesis drugs, there is plenty of enthusiasm for the field.
Folkman, meantime, is focused on results. He is encouraged by
success over the past decade treating children with
life-threatening hemangiomas—masses of blood
capillaries—with interferon-alpha, an older drug that has
anti-angiogenic properties. As he projects before and after
photos of tiny patients on the wall—the baby in a checked
shirt, the girl in a red-flowered dress—Folkman maintains his
quiet calm. But joy is all over the place. “Look,” he says, “at
what we’ve learned.”
BLASTING THE SUPPLY LINES
As trials continue, scientists will learn more about how
best to use the new drugs. In combination with chemotherapy
and radiation (which go after tumor cells), a strike against the
enemy could be much more powerful—blasting not just troop
headquarters, but the supply lines, too.
One day, doctors
might be able to take a
tumor’s thumbprint by
testing urine, blood or
tissue for the angiogenesis
proteins that are busy
recruiting blood
vessels—then prescribe a
cocktail of inhibitors that
would stop them in their
tracks. The drugs might
even be given long term to
prevent tumors from
surging back—a still
unsolved and endlessly
frustrating challenge in treatment. “If we can’t cure cancer, I
would be very willing to turn it into a chronic disease,” says
Dr. James Pluda of the National Cancer Institute. “These drugs
have that kind of potential.”
And there is potential, too, for angiogenesis drugs to play
a role in a host of other illnesses, including heart disease. Near
the elevators leading out of his lab, Folkman lingers to talk,
never tiring of his subject. “You have to think ahead,” he says.
“Science goes where you imagine it.” We can only imagine it
will get better and better.
© 2001 Newsweek, Inc. |
