eBAWIS Chapter Meeting at Novartis

****Thank you to E & K Scientific for In-kind Support of this Event****

East Bay AWIS March Chapter Meeting – March 22, 6:30-8:30 pm

Inhibition of tumor invasiveness and metastasis by combined c-Met and VEGF blockade

Barbara Sennino, PhD   

Most angiogenesis inhibitors used in the treatment of cancer block the actions of VEGF, a cytokine that promotes blood vessel growth and survival.  Treatment with the monoclonal anti-VEGF antibody bevacizumab, usually administered in combination with chemotherapy, delays progression and prolongs survival of some patients, yet many tumors eventually progress. Preclinical studies have shown that inhibition of VEGF signaling promotes invasiveness and metastasis in some tumor models. The mechanism underlying this form of resistance is not fully understood, but vascular pruning, intratumoral hypoxia, and increased expression of c-Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF), could be contributing factors. We asked whether selective VEGF inhibition is sufficient to increase invasion and metastasis and whether selective c-Met inhibition is sufficient to block this effect. We found that hypoxia, HIF-1alpha, and c-Met mRNA, protein, and phosphorylation were increased in spontaneous pancreatic neuroendocrine tumors treated with a function-blocking anti-VEGF antibody.  Importantly, invasion and metastasis accompanying anti-VEGF therapy were blocked by administration of c-Met inhibitors. These results show that selective inactivation of VEGF reduces tumor growth but can lead to greater invasiveness and metastasis in mice.  However, inhibition of VEGF and c-Met together not only slows tumor growth but also decreases tumor invasiveness and liver metastasis and prolongs host survival.

Dr. Barbara Sennino is a cancer and vascular biologist. She earned her PhD in Italy and then joined the laboratory of Dr. Donald McDonald at UCSF. Her research has been focused on tumor angiogenesis and the cell-to-cell signaling and growth factor crosstalk between blood vessels and tumor cells. Over the past few years her interest has been centered on elucidating mechanisms by which tumor cells become invasive and metastasize to other organs and how these processes are affected by anti-angiogenic therapy. In collaboration with academic groups and pharmaceutical companies, she is currently studying the mechanisms underlying tumor regression and therapeutic resistance with the goal of guiding the development of novel therapeutic targets that can prevent and stop tumor cell aggressiveness and dissemination.

When:  March 22, 2012  6:30-8:30 pm

Light supper provided

Where:  Novartis,  5400 Hollis St, Building X-310 Emeryville, CA

Directions ,  Free Parking in front of building

Register  at http://ebawismarchsennino.eventbrite.com
$5/members  $10/nonmembers  to be collected at door

Scientists and Science Enthusiasts, Men and Women,  Members and Non-members Welcome!

****Thank you to E & K Scientific for In-kind Support of this Event****