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Tumor Angiogenesis: VEGF Pioneer Honored as Quest for Answers Persists

Anita T. Shaffer @Shaffer1
Published: Friday, Nov 18, 2011
Bevacizumab antibodies

Bevacizumab antibodies released into pathologic angiogenesis.

The scientific strategy of attacking cancer by thwarting angiogenesis has been on a roller coaster ride for the past 40 years, with reactions in oncology research circles ranging from soaring hopes to a current flattening of expectations.

Yet the characterization of vascular endothelial growth factor (VEGF), which is the target of many antiangiogenic therapies, marks an advancement in the understanding of blood vessel development that has paved the way for 5 new oncology drugs, as well as 2 drugs for the treatment of ocular disorders since 2004 (TABLE).

Those were the sentiments that prominent researchers expressed recently as they applauded Napoleone Ferrara, MD, a Genentech scientist credited with isolating and cloning VEGF and building the humanized monoclonal antibody that led to the development of bevacizumab (Avastin) and ranibizumab (Lucentis).

Ferrara received the Dr Paul Janssen Award for Biomedical Research, which Johnson & Johnson sponsors in honor of the late scientist who played a major role in drug development at the company and elsewhere for 50 years. Ferrara was chosen for the award, which carries a $100,000 prize, by an independent panel of scientists, and was recognized during a September 14 symposium at the New York Academy of Sciences.

Napoleone Ferrara, MD

Napoleone Ferrara, MD, of Genentech, is the seventh recipient of the Dr Paul Janssen Award for Biomedical Research.

It is the latest in a series of awards for Ferrara, whose honors include the 2010 Lasker-DeBakey Clinical Medical Research Award.

In the context of cancer research, Ferrara’s work has paved the way for significant advances.

“Dr Ferrara’s discovery of VEGF transformed what we know about blood vessel development,” said Solomon Snyder, MD, a professor of Neuroscience, Pharmacology, and Psychiatry at Johns Hopkins School of Medicine in Baltimore, Maryland, and chair of the Janssen award selection panel, in announcing the honor earlier this year.

“What’s extraordinary here is the diversity of antiangiogenic VEGF pathway–targeting drugs that have been approved,” said Robert S. Kerbel, PhD, a professor at the University of Toronto in Canada, during the symposium. “That’s an amazing achievement in medical oncology.”

The recognition comes at a time when the complexities surrounding antiangiogenic approaches to fighting cancer continue to unfold as researchers seek to answer challenging questions about how such drugs affect patients and why they often do not demonstrate significant gains in overall survival, particularly in breast cancer where the utility of bevacizumab has been hotly debated.

FDA-Apppoved VEGF Therapeutics

Oncology

Drug Description Indications FDA Approval
Bevacizumab
(Avastin)
Genentech
Humanized monoclonal antibody Metastatic colorectal cancer
Non–small cell lung cancer
Metastatic breast cancera
Glioblastoma
Metastatic renal cell carcinoma (RCC)
2004-2009
Pazopanib
(Votrient)
GlaxoSmithKline
Tyrosine kinase inhibitor (TKI) Advanced RCC 2009
Sorafenib
(Nexavar)
Bayer/Onyx
TKI Advanced RCC
Unresectable hepatocellular
carcinoma
2005-2007
Sunitinib
(Sutent)
Pfizer
TKI Advanced RCC
Gastrointestinal stromal tumors
Pancreatic neuroendocrine tumors
2006-2011
Vandetanib
(Caprelsa)
AstraZeneca
TKI Medullary thyroid cancer 2011

Eye Disease

Ranibizumab
(Lucentis)
Genentech
Recombinant humanized
IgG1 kappa isotope
monoclonal antibody fragment
Neovascular age-related
macular degeneration

Macular edema following
retinal vein occlusion
2006-2010
Pegaptanib
(Macugen)
Eyetech
Pegylated modified oligonucleotide (aptamer) Neovascular age-related macular degeneration 2004

a Indication remains on label pending final decision by FDA commissioner on recommendation to revoke.
VEGF indicates vascular endothelial growth factor; IgG1, immunoglobulin G1.

Ferrara himself noted that he is still learning about VEGF after nearly 2 decades of research. “There are so many questions that have been left unanswered,” he said.


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