Napoleone Ferrara, Genentech Fellow

Ferrara and his team identified the gene for vascular endothelial growth factor (VEGF) more than 15 years ago. They characterized the VEGF protein as the major regulator of physiologic angiogenesis in embryonic development, reproductive biology, endochondral bone formation, and wound repair. In addition, they demonstrated that VEGF is a key mediator of pathologic angiogenesis in certain tumors and ocular disease. These studies led to the development of a humanized anti-VEGF antibody, Avastin® (bevacizumab), as a therapy for solid tumors. Avastin received U.S. Food and Drug Administration approval in February 2004 for use in combination with intravenous 5-Fluorouracil-based chemotherapy as a treatment for first-line metastatic colorectal cancer and in October 2006 for use in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer. In 2005, positive Phase III clinical data were also reported for Avastin in metastatic breast cancer. A related anti-VEGF antibody fragment, Lucentis®(ranibizumab injection), also demonstrated clinical benefit in patients with the wet form of age-related macular degeneration. In June 2006, Lucentis was approved by the FDA for the treatment of neovascular (wet) age-related macular degeneration.

Angiogenesis

A diagram illustrating the role of VEGF in the formation of new blood vessels that support tumor growth.

The Angiogenesis group has developed numerous reagents and pre-clinical animal models in order to better understand the mechanisms of resistance or escape from anti-VEGF therapy. The group also works to characterize how new targets, pathways, or even cytotoxics might have synergistic activity when used alone or in combination with Avastin. We are using an array of biomedical imaging technologies and more conventional cellular and histochemical markers to evaluate effects of treatment on a tumor and its vasculature.

The group also has a diverse pipeline of next-generation anti-angiogenic agents. These antibodies target other components of the VEGF axis, such as related ligands, receptors or co-receptors, such as the neuropilins. Other targets function up- or down-stream of VEGF or through parallel pathways and have the potential to work either alone or in combination with existing anti-angiogenic therapies.