Here's what ABC had to say about anti-angiogenesis research: "Cure" is still a Four-Letter Word in Cancer Research Drugs Destroy Mouse Tumors
By Jenifer Joseph ABCNEWS.com May 4 - Two rooms in Dr. Judah Folkman's research lab provide a side-by-side cautionary tale on the rocky road of cancer research. In one room, there are cages holding hundreds of frisky, healthy mice whose cancer tumors were completely eradicated by a new drug combination. But in the next room is a stack of three-inch-thick books filled with the dashed hopes of cancer-drug experiments that were tried and failed. The books serve as a reminder to his research team at Boston Children's Hospital, that what can be the definitive cure for cancer in mice often turns out to be useless in humans. And people are the reason Folkman never uses that word-cure-when talking about his own work. Still, Folkman's revolutionary work has many in the scientific community jumping for joy. The National Cancer Institute, for one, has already declared the development of the drugs, called angiostatin and endostatin, one of its top priorities. Dr. James Watson, a Nobel laureate and director of the Cold Spring Harbor cancer research lab in New York, told The New York Times: "Judah is going to cure cancer in two years."
Starving Cancer Tumors The drugs Folkman is experimenting with work by choking off the supply of blood vessels that tumors need to flourish. In a process called angiogenesis, arteries spring up like weeds around a tumor and fuel its growth. Angiogenesis inhibitors, also called anti-angiogenesis drugs, stop arterial growth and starve the tumor. Dr. Jim Pluda, an oncologist at the National Cancer Institute (NCI) who is overseeing anti-angiogenesis research, compares the approach to trying to eliminate dandelions from a lawn. "Normally we keep whacking off the top and the dandelion keeps growing back," he says. "But if you kill the roots, the whole plant dies." Pluda calls Folkman's research "very impressive and compelling." But he and other experts point out that it is still only mouse data; clinical trials on humans are at least a year away. "The field of oncology," adds Pluda, "is littered with the bodies of agents that were the next cure for cancer."
Dangerous Downsides? Indeed, researchers have a number of major hurdles to overcome. For example, if the drugs block the creation of blood vessels in order to kill tumors, could they also damage other, essential blood vessels in the process? Dr. Robert Auerbach, a University of Wisconsin angiogenesis expert who has worked with Folkman since the early '70s, points out that patients with heart conditions take drugs that promote the growth of extra blood vessels to improve blood flow to the heart. A healthy supply of blood vessels is also important during childhood growth stages and menstruation and in wound healing. "There might be a transient effect of the (anti-angiogenesis) drugs," says Auerbach. "In other words, they may kill tumors but also stop wounds from healing." But he adds that we still don't fully understand the factors involved in blood vessel production. Another issue, he says, is that drugs don't often stay in the human body as long as they do in mice. So while the combination of drugs might totally kill off tumors in mice, that might not happen in people. Despite the fact that these fundamental questions have yet to be answered, the allure of the magic bullet is obviously powerful: The Times story appeared on Sunday, and today, more than 300 cancer patients called Folkman's office looking for help, and the stock price of the drugs' maker, EntreMed, rocketed 378 percent. Reuters contributed to this report.
Other Anti-Angiogenesis Research Sugen, a biotech company, is testing a compound called "SU5416" and is currently in the first phase of human trials. Lead investigator Lee Rosen, at UCLA Medical Center, says the work is still early but shows promise. Magainin is testing "squalamine," a synthetic compound originally found in shark livers. Human testing has begun, and data will be presented in the fall. So far, researchers say they've successfully prevented growth of brain, lung and breast cancer, as well as melanoma, in animal trials. Genentech is working on human tests of an antibody, named anti-VEGF, that knocks out a growth factor needed for new blood vessels to sprout. Results will be reported at the American Society of Clinical Oncology meeting this month. Entremed, the company producing endostatin and angiostatin, is also testing thalidomide in humans. Thalidomide, which was marketed as a sedative in the 1960s, was found to cause horrific birth defects because it blocked blood vessel formation in pregnant women. But for that very reason, the drug appears to be a tough tumor killer. |