A new generation of cancer drugs and a successful treatment for an eye disease that can lead to blindness are the fruits of two decades of work by former UCSF postdoctoral fellow and current Genentech scientist Napoleone Ferrara, MD, who has just been named the winner of a Lasker Award, the premier US biomedical research prize.
The Lasker Foundation announced on Sept. 21 that Ferrara has won the 2010 Lasker-DeBakey Clinical Medical Research Award, which includes $250,000, for his studies of new blood vessel growth that led to the new disease treatments. The growth of new blood vessels is vital for tumor growth. Uncontrolled blood vessel growth also plays a role in wet macular degeneration, a form of the disease that is a common cause of blindness in the elderly.
Over many years, Ferrara parlayed basic research studies, started at UCSF, into the successful development of two drugs that are similar to each other. One is Avastin, now used in treatment regimens targeted against certain types of lung, colon, brain, kidney and breast cancer. The other is Lucentis, used to treat wet macular degeneration.
Ferrara was hot on the trail of the molecule from which his most noteworthy achievements stem while he was still at UCSF. Trained in his native Italy as a physician specializing in endocrinology, Ferrara came to the United States in 1983 as a postdoctoral fellow. He worked in the laboratories of two UCSF researchers who were conducting pioneering studies on new blood vessel growth, a process that scientists call angiogenesis.
“Napoleone came to my laboratory to study changes in blood vessels in tumors,” says neuroendocrinologist Richard Weiner, PhD, UCSF professor emeritus in the Department of Obstetrics, Gynecology and Reproductive Sciences.
Weiner’s lab group had found that tumors of the pituitary gland grow new blood vessels. Even the normal pituitary has a very rich supply of blood, Weiner says. “It made sense to look for cells that make angiogenic factors in the pituitary.”
While attempting to grow capillary cells from the pituitary to use in a test to detect growth factors, Ferrara ended up also growing a different type of pituitary cell, called the folliculostellate cell, in lab cultures. These cells stimulated blood vessel growth, and Ferrara set out to find the factors responsible.
He isolated three angiogenic signals via chemical separation techniques. Two were the basic and acid fibroblast growth factors, already recognized as angiogenic factors by the work by others, especially former UCSF faculty member Denis Gospodarowicz, PhD, in whose UCSF lab Ferrara also later worked.
“To his credit, Napoleone saw this third peak, and he never let go of that,” Weiner says.
After leaving UCSF to join Genentech in 1988, Ferrara identified and cloned the human gene for the third protein in 1989. The protein is called vascular endothelial growth factor, or VEGF. Ferrara subsequently led efforts to make molecules – culminating in the drugs Avastin and Lucentis – that could target VEGF and inhibit its ability to spur blood vessel growth.
Lucentis, which can improve vision in patients suffering from wet macular degeneration, was approved by the Food and Drug Administration in 2006. Avastin has been approved for several cancer indications since 2004.
“He has done an incredible amount of work,” Weiner says. “He is a brilliant scientist, and I’m very proud that he worked in my lab.”
Several UCSF researchers and others trained at UCSF have been involved in the drug development and clinical trials conducted to test these drugs, a testament to UCSF’s expertise in translating research discoveries into valuable treatment for patient care.
UCSF Chancellor Susan Desmond-Hellmann, MD, MPH, former president of product development at Genentech, oversaw the development of the drugs. As a Genentech employee, Robert Kim, MD, UCSF associate clinical professor of ophthalmology, directed clinical trials for Lucentis. UCSF physicians have participated in clinical trials for both Lucentis and Avastin.
Other 2010 Lasker Award winners include Douglas Coleman, PhD, retired from the Jackson Laboratory in Bar Harbor, Maine, and Jeffrey Friedman, MD, PhD, from Rockefeller University in New York City, who will share the Albert Lasker Basic Medical Research Award for work on the hormone leptin, which plays a role in appetite and obesity.
David Weatherall, MD, of the University of Oxford in the United Kingdom won the Lasker-Koshland Special Achievement Award in Medical Science for studies of thalassemia, a blood disease arising from mutations in a gene that encodes the hemoglobin protein.