By Jocelyn Selim

Hope in the Pipeline

By Jocelyn Selim

The promise of angiogenesis research is the creation of an entirely new class of cancer drugs that specifically target the blood vessels sprouting into tumors to feed their growth. This means that the therapies’ side effects should be less toxic than those of traditional chemotherapy, which can affect almost any of the body’s cells—whether healthy or diseased, explains William Li, the president of the Angiogenesis Foundation, a Cambridge, Mass., nonprofit organization of physicians, scientists and patient advocates who are dedicated to advancing angiogenesis research.

Anti-angiogenic drugs generally fall into one of two categories. One type is made of proteins known as monoclonal antibodies. These drugs interfere with certain biochemical signals—known as angiogenic growth factors—that encourage a tumor to recruit blood vessels, or they block the receptors on blood vessels that usually bind to these growth factors. The monoclonal antibodies thus block the biochemical “conversation” that encourages blood vessels to grow and support a tumor. The other main category of anti-angiogenic drugs is small-molecule tyrosine kinase inhibitors. These also bind to angiogenic growth factors’ receptors, though not to the growth factors themselves. Other drugs, like the half-century-old medication thalidomide, have also been found to have powerful anti-angiogenic properties, but how they work is still not fully understood.

So far, the U.S. Food and Drug Administration (FDA) has approved at least eight anti-angiogenic cancer therapies. These include two monoclonal antibody drugs, Avastin (bevacizumab) and Erbitux (cetuximab), for treating colorectal, lung, breast, or head and neck cancers. Three tyrosine kinase inhibitors are approved to treat lung, kidney, liver, pancreatic or gastrointestinal tumors: Nexavar (sorafenib), Sutent (sunitinib) and Tarceva (erlotinib). Thalidomide and Revlimid (lenalidomide) are approved for the treatment of multiple myeloma. Torisel (temsirolimus), a drug known as an mTOR inhibitor, is approved for advanced renal cell carcinoma.

According to Li, these drugs are just the beginning. “There are 130 anti-angiogenesis drugs currently in human testing,” he says. “Over the next decade, we’re going to see a fleet of these drugs reach the market, and they are going to change the way cancer is treated. And they all go back to one man, Judah Folkman.”