By Ben Harder
Targeting Cancer Through Its Roots
What is angiogenesis and why are cancer researchers studying it?
By Ben Harder
For a gardener who’s aiming to clear out a weed, the roots are natural targets. If she can remove them, the plant is finished. And if she can’t, they might aid her in poisoning the weed, because the roots can absorb herbicides from the soil.
Just as roots supply plants, blood vessels act as conduits for nutrients and oxygen. Tumors and healthy tissues alike rely on these vessels.
Angiogenesis, from the Greek words meaning “vessel birth,” is the process by which new blood vessels emerge. These vessels form more or less stable networks in most parts of the body. But in and around malignant tumors, molecules made by cancer cells encourage new blood vessels to sprout sloppily and feed the growing malignancy.
Left: A tumor (tan) produces growth factors (yellow) that partner with receptors (orange) on blood vessels. This partnership stimulates the growth of new, though abnormal, blood vessels to nourish the tumor. Research suggests that little chemotherapy (green) can make its way through these defective blood vessels to poison the tumor. Right: The drug Avastin (blue) blocks growth factors from turning on their receptors. Research suggests that some of the faulty blood vessels begin to die off. Others form in a more orderly structure, which as a result improves both the delivery and the effectiveness of chemotherapy. [Art: Nicolle Rager Fuller]
Researchers have determined that drugs which stop or reverse the growth of tumor-generated vessels can be powerful tools against cancer. Three such drugs—Avastin (bevacizumab), Nexavar (sorafenib) and Sutent (sunitinib)—have been approved recently in the United States.
“These are three new therapies that simply didn’t exist three years ago,” says medical oncologist George W. Sledge Jr. of Indiana University Cancer Center in Indianapolis. He and other researchers predict that even more drugs are on the way, and that those treatments might eventually be used against virtually every kind of cancer.
“This has opened up a whole new vista for patients,” Sledge says.
For now, however, the new drugs have been approved to treat only advanced cancers of a few specific organs, including the colon, rectum, breast, lung and kidney. Most patients also receive other treatments such as surgery and radiation, and there’s no sign that that will change soon.
Someday, however, blood vessel–inhibiting drugs may be used in addition to surgery, chemotherapy and radiation to treat a wide range of cancers, says Judah Folkman, a surgeon and cancer biologist at Children’s Hospital Boston. Folkman envisions a future in which the new class of drugs could be used to control cancer much as antibiotics are now widely used to fight bacterial infections. That forecast comes from the doctor who, three and a half decades ago, first recognized the important role that vessels play in feeding tumors.
Tiny tumors are common, even in healthy people, Folkman says. “Almost everyone has these.” But these clusters of cancerous cells never grow beyond the size of a pinhead unless they are connected to a blood supply, Folkman found in the 1960s.
“About one out of 600 of them begins to recruit blood vessels,” he says. That transition, known as the angiogenic switch, creates a dangerous tumor that’s likely to grow and could also metastasize throughout the body.