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Study sheds light on angiogenesis inhibitors, points to limitations, solutions
Date:3/2/2009

er at the Catalan Institute of Oncology-IDIBELL, in Spain.

In addition to their call for more studies of angiogenesis inhibitors' effects, the researchers encourage more research to identify the mechanisms underlying cancer's resurgence after initial success with the angiogenesis inhibitors. They suspect that the increased invasion and/or metastasis is the tumor's response to starvation induced by the drugs.

"A well vascularized tumor is well fed and happy," Hanahan says. "It has no driving force to become more invasive. We hypothesize from the mouse models that if you cut off the tumor's blood supply this drives the cancer to become more invasivemore metastatic as it seeks more oxygen and nutrients."

The Cancer Cell paper extends earlier findings reported by Casanaovas, Hanahan and Bergers in 2005 and 2008 (Casanovas O. et al. Cancer Cell 2005; Du R. et al. Cancer Cell 2008), and it appears along with one by another research team from Robert Kerbel and colleagues at the University of Toronto, also reporting evidence of increased metastasis in mice treated with anti-angiogenesis drugs. In August, 2008, Bergers and Hanahan reviewed all of the recent research addressing resistance to angiogenesis inhibitor therapy in the journal Nature Reviews Cancer.

The scientists tested the effects of the anti-angiogenic drug sunitinib (manufactured as Sutent) in mouse models of both pancreatic neuroendocrine cancer and glioblastoma, the most common type of primary brain tumor. In both cancers, they found that treated tumors shrank or stabilized but did not disappear during the first weeks of treatment. But after this initial benefit, they detected an adaptive response by the tumor. The glioblastomas increased invasion into adjacent normal tissue. The pancreatic tumors also became more invasive and, in addition, metastasized to the liver.

"Our animal studies are consistent with some clinical results that human
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert  

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