Dr. Napoleone Ferrara is a world renowned molecular biologist in the field of angiogenesis. Dr. Ferrara was first recognized for the discovery of vascular endothelial growth factor (VEGF) and the development of the first anti-VEGF antibody. These findings paved the way for the development of the first clinically available angiogenesis inhibitor, bevacizumab (Avastin®). Avastin, which inhibits blood vessel growth and suppresses cancer tumor growth, has become part of standard treatment for a variety of cancers. Dr. Ferrara also co-discovered the role of VEGF in retinal disease and developed the monoclonal antibody ranibizumab (Lucentis®). Lucentis is highly effective at preventing vision loss and is used as a first-line therapy for the treatment of the wet form of age-related macular degeneration and other related disorders.
During his highly esteemed career, Dr. Ferrara has earned dozens of scientific achievement awards. Most notably was the prestigious Lasker-DeBakey Clinical Medical Research Award, which he received in 2010 for his discovery of VEGF. The Lasker-DeBakey award is often referred to as the “American Nobel” as 79 Lasker recipients have been awarded the Nobel Prize. More recently, Dr. Ferrara received The Economist’s Innovation Award for Bioscience in 2012 and the Breakthrough Prize in Life Sciences in 2013. Dr. Ferrara is currently serving as the Senior Deputy Director for Basic Sciences at the University of California, San Diego School of Medicine and is a Distinguished Professor of Pathology at UCSD’s Moores Cancer Center.
Q: How did you start working on VEGF?
NF: Well, that was actually the work that I started when I was a postdoc. Before Genentech, I was a postdoc at UCSF. I was studying pituitary cells, and I discovered that certain cells in the pituitary gland produce factors that can induce endothelial cell growth. I was very fascinated by this result. I did a second postdoc in a different lab at UCSF where I learned protein biochemistry and tried to isolate VEGF. At Genentech, we completed this work. It was a very long process.
Q: Can you talk about your experience at Genentech with developing Avastin?
NF: I joined Genentech in 1988. I got hired because I had a background in reproductive endocrinology. So I was working in a completely different field there on a reproductive drug, which ended up actually have no effect. But aside from the mainstream work, Genentech gave people free time to pursue their own research interests. For me, it was VEGF. First we attempted to isolate and characterize VEGF, which took us several years. We began with the basic science such as isolating, sequencing, cloning, and characterizing VEGF. It was a very exciting time. And then we needed to convince ourselves that this was something that was worth testing in humans. Genentech is a great place to do research. It has wonderful facilities and technology, which allowed us to answer some of these questions. After years of work, we developed the humanized antibody, Avastin. Avastin entered the clinic in 1997.
Q: What are new angles for therapeutic angiogenesis and anti-angiogenesis?
NF: That’s a great question. There was lots of excitement about therapeutic angiogenesis a decade ago. There was the hypothesis that we could take an angiogenic factor and make new blood vessels to treat ischemia. However, most of the clinical trials were negative. Therapeutic angiogenesis is not nearly as advanced as the anti-angiogenesis field. For anti-angiogenesis, the new angle I think is to find a better therapeutic combination, for example, a combination cancer immunotherapy.
Q: What is the challenge for targeting angiogenesis in cancer?
NF: We still don’t completely understand the angiogenic mechanisms among different tumors. For some kinds of tumors, it is more amenable to provide anti-angiogenic therapy. For example, renal cancer cells are more amenable to anti-angiogenic therapy than pancreatic cancer cells. And this phenomenon cannot be predicted by the preclinical data. I mean, in mouse models, anti-angiogenesis therapy almost always shows a uniform response. So one of the goals of the field is to discover tissue specific biomarkers.
Q: After 25 years at Genentech, why did you decide to go back to academia? What are your current research goals?
NF: The reason that I went back to academia was because I wanted to try different things. One thing that was difficult at Genentech, which comes with being a part of a company, was to collaborate with other people. That’s why I joined UCSD in 2013. The goal of my lab is to continue the research that I’ve done so far in angiogenesis. There are still a lot of things to do in this field. The research I did previously brought some successful drugs to market, such as Avastin, Lucentis, and other VEGF inhibitors. We learned a lot about what you can accomplish by blocking angiogenesis. We also understood the limitation of these drugs. Some patients respond better than others, and some patients become resistant. So I think this is one of the lines of research I want to pursue at UCSD. We need to have a greater understanding of this process, so that we can develop additional strategies and identify novel targets. I think it’s a wonderful field.
Q: What are the pros and cons of working in industry?
NF: When I joined Genentech, I think the company had an extremely high level of science and technology. It was very appealing to me at the time. I think one of the cons for big companies is that priorities can change. For me, I was very fortunate that I could study what I liked at Genentech and have a very stable career. I worked on my favorite project in Genentech for 25 years. But some people might not be so fortunate, because sometimes, great science is not easy to translate. This is a big drawback. So you have to be very flexible.
For more on Dr. Ferrara and his exciting work with VEGF, check out Dr. Ferrara’s interview with the International Journal of Developmental Biology.