Angiogenesis and cancer
Taming tumors by cutting off their blood supply
by Hilary F. Bennett
ven the most ferocious lion, weakened by starvation and imprisoned in a cage
with no means of escape, would be as harmless as a newborn kitten.
Like that lion, a malignant tumor, if deprived of access to blood vessels through which essential nutrients and oxygen can be delivered and its cells can escape to other sites in the body, is virtually harmless. In fact, without an adequate network of blood vessels, a tumor can grow no larger than a pea, trapped in a steady state of submission.
But, unfortunately for the millions of people with cancer, tumors usually manage to break free of their prison. They send out a distress call — a powerful chemical signal to nearby blood vessels — stimulating them to cast out lifelines in the form of new, hair-thin capillaries that migrate to and permeate the tumor.
This process of new blood vessel development, called angiogenesis, normally takes place only during fetal development, wound healing, and the menstrual cycle, but tumors can subvert it for their own sinister purposes. And once a tumor has its own network of blood vessels, it can grow, spread, and, as many cancer patients know all too well, do great harm.
A revolutionary hypothesis
Today, the notion that tumors are dependent on angiogenesis to grow and spread is widely accepted, but it was not always so. Surgeons had noted since the nineteenth century that a tangled thicket of blood vessels permeated the tumors they removed from cancer patients, but chalked it up to an inflammatory response.
Without an adequate network of blood vessels, a tumor can grow no larger than a pea, trapped in a steady state of submission.
In the 1960s, while doing research for the U.S. Navy, a young surgeon and draftee named Judah Folkman, M.D., proposed another explanation based on some observations he had made in the lab — that the blood vessels in tumors were not an irrelevant byproduct of tumor development, but were essential to its ability to grow and ultimately spread. If, Folkman speculated, one could stop the new blood vessels from forming, perhaps the tumor could be prevented from growing and spreading.
For many years, this revolutionary hypothesis was widely scoffed at by the research community. But Folkman, who directs the Surgical Research Laboratories at Children's Hospital Boston, was convinced he was on to something important and spent many years in the laboratory relentlessly pursuing his ideas.
Folkman's perseverance paid off. In the early 1980s, he and his colleagues identified the first molecule that induces angiogenesis and, a few years later, the first of many agents that inhibit it. Their hope was to develop a novel way of fighting cancer by halting the formation of the new blood vessels tumors need to thrive, rather than by attacking the tumor cells directly, which is the strategy of chemotherapy and radiation therapy.
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