Cutting off cancer's supply lines.

Targeting the blood vessels that feed tumours is not the silver bullet once hoped for, but refinements to the strategy may suggest further ways to treat the disease. Erika Check Hayden reports. Drugs that aim to choke off a tumour's blood supply, known as angiogenesis inhibitors, have been hailed as opening a new era in cancer therapy. But a flurry of animal studies suggests that such drugs may in certain situations actually accelerate the spread of cancer. "We're just finding the limitations of these types of agents in the clinic," says John Ebos, a cancer researcher at the University of Toronto, Canada. "I don't think it's unique — various types of therapies, such as chemotherapy and radiation, also have limitations. It's just a question of how we can overcome it." This is a key time in the long and controversial history of these drugs. In May, the US Food and Drug Administration (FDA) is expected to decide whether to expand use of bevacizumab, the first angiogenesis inhibitor. This monoclonal antibody, sold as Avastin by South San Francisco-based Genentech, was approved in 2004 for treating metastatic colon cancer in combination with chemotherapy. It has since been approved in the United States and elsewhere for other uses, and on 31 March an FDA advisory committee recommended the drug also be approved for glioblastoma, a deadly brain cancer for which few other treatments are available. The agency's decision is expected in May. According to regulatory papers filed in January, Genentech may before then reveal results of a clinical trial to test the use of bevacizumab as an 'adjuvant' used with chemotherapy in patients whose colon tumours have been surgically removed. The 2,710-patient phase III trial investigated whether those who take bevacizumab are more likely to survive without recurrence of their disease than patients who do not take the drug. "There are tens of thousands of patients with early colorectal cancer who don't get Avastin right now," says Geoffrey Porges, an analyst with Sanford C. Bernstein in New York City. Success as an adjuvant therapy "would open up a market at least as large as the current metastatic market", he thinks, noting that trials testing the drug as an adjuvant for other cancers are under way. Last year, the drug racked up $4.8 billion worldwide in sales; its wholesale price is about $50,000 per year of treatment. The original idea behind bevacizumab and other …