Dr. Kevin PinneyAssociate Professor of Chemistry
Generals call it siege -- obliging an enemy fortress to yield or starve. Baylor University's Kevin Pinney calls it vascular targeting.
The enemy he hopes one day to besiege and conquer: solid Tumor cancers. Cancers of the prostate, the ovaries, the breast, the thyroid glands. A general, where he can, cuts off supplies of food and ammunition. Kevin Pinney's aim, as a synthetic organic chemist specializing in cancer, is to deny tumors the oxygen and nutrients they need for survival and growth. He's persuaded that he and fellow researchers are moving swiftly toward success.
Think of the body's fluid-carrying vessels as the rivers and canals keeping a tumor well-supplied and deadly. Closing down the supply routes means -- in medical terms -- developing agents that selectively target and disrupt blood flow to old and new vessels alike.
No blood, no oxygen -- no tumor. So goes the theory, well-substantiated by now. Kevin Pinney is more than ready to subject it to human clinical trials.
File away for future reference the name of these disruptive devices: Vascular targeting agents; VTA's, for short.
"We're not worrying about getting into the tumor cells," explains Pinney, associate professor of chemistry and co-founder of Baylor's Center for Drug Discovery. "We're just going to shut down the blood flow. If we shut down the blood flow, we shut down the supply line for nutrients, we shut down the oxygen -- all those things. And we can kill those cells. And one vessel feeds hundreds of thousands of those tumor cells. It's really a paradigm shift."
Or, as generals might put it, a strategy flip-flop. What you can't destroy fast enough in open combat, you eliminate by other means. As with conventional war, so with the war on disease -- a war that made of Kevin Pinney a researcher and teacher rather than, more predictably perhaps, a cancer doctor.
"Probably since I was in high school," he reflects, "I have had an interest in doing something in the cancer area to help patients. It was just sort of a personal calling I have felt through the years. Of course I considered medicine, and I thought that would be extremely fulfilling; but I always thought that with some patients you would end up at a point where there were no further drugs to treat the cancer they had. You know - your arsenal of weapons is exhausted."
So much for open combat. What, then, Dr. Pinney?
"I thought maybe the way I could approach this was to combine my interest in chemistry and science with trying to go the route of drug development; in other words, working on the cancer problem from the point of trying to develop new treatment agents that then would go into this arsenal that we have established worldwide for cancer."
This wasn't about intellectual curiosity and nothing else. It was about curiosity plus vocation -- the sense of an supernatural elbow in the ribs.
"In my own personal life I'm a strong Christian," says Pinney. "I had thought about ways I could use what talents God had given me, and I just had felt from a very young age a strong interest that I attribute to God nudging me in that direction in the cancer area."
With a doctorate from the University of Illinois in 1990, Pinney moved into postdoctoral work at the University of South Carolina, funded by the National Cancer Institute. Baylor, three years later, beat out stiff competition for his academic services.
"I came here," Pinney recalls, "with the idea of trying to make a difference in cancer through synthetic organic chemistry." He liked the "really excellent students" and the "friendly atmosphere." Moreover, the university was forthcoming with start-up money for his research.
Pinney began at this point a fruitful collaboration with a distinguished Arizona State University chemist working on related problems. George R. "Bob" Pettit -- who by Pinney's reckoning deserves the Nobel Prize -- became not just a long-distance co-worker but also a close friend, despite generational distinctions. Of Pettit the younger scientist says: "He just gets up every day wanting to help cancer patients. A phenomenal human being." The two have collaborated formally since 1994.
It was Pettit who discovered the compound Combretastatin A-4 Phosphate (CA-4P) -- a natural product and exceptionally promising vascular targeting agent now in human clinical development by Oxigene, Inc., a NASDAQ-listed biopharmaceutical company in Waltham, Mass. "That compound is doing very well in the clinic --not approved yet for sale, but it's getting closer and closer every day."
Pinney and Pettit are part of an informal network of scientists (including Baylor professors Christopher Kearney and Mary Lynn Trawick) working to win a federal green light for their researches into vascular targeting. Baylor students have a part in it, too, through participation in Pinney's compound-making research group in the chemistry department. Two Baylor-manufactured compounds are presently licensed to Oxigene for development.
"It's really good for the student to see the whole process," Pinney says, "to see [in drug development] how the chemistry comes together, the biology comes together; [also] public perception, finances, intellectual property."
Follow a scientific trail far enough and new, unexpected sights come into view -- "sights," sometimes, in the literal sense. A scientific/medical foxhunt seeking to run down cancerous tumors inspires research with implications for the treatment of macular degeneration and other eye diseases Vessels sometimes grow in the retina, where they shouldn't, explains Pinney. A laser can't knock them out permanently or for that matter reverse harm already done. Evidence, he says, suggests that VTA's not only can shut down the offending vessels but even undo some of the damage already wrought.
The siege, plenty hot as it was, gets hotter. The indicated victor: science.