At Norris Cotton, Radu Stan and Steve Fiering take a promising path in the fight against cancer
In a lab on the 6th floor of the building that houses the Norris Cotton Cancer Center, Radu Stan and Steve Fiering are quietly exploring a novel end-run around one of the great disappointments in the effort to fight cancer.
For the last 40 years, researchers have been focused on the idea that if you can disrupt a tumor's ability to feed itself through new blood vessels, you can destroy it. "They’ve all failed," says Stan. "If you starve the tumor of blood vessels, the bulk will die, but whatever is left will become even nastier."
Stan and Fiering are onto a different approach. They're experimenting on a protein that seems to help tumor cells evade the body's immune system. Suppress the protein, they've found, and you suppress tumor growth. If you've ever wondered where the money goes that you or your friends or relatives or neighbors raise for The Prouty, it's into pathbreaking work like this.
Stan, an MD, grew up in Romania; Fiering, an immunologist, in New Jersey. Both teach at Dartmouth and at the Geisel School of Medicine. Though neither started out in cancer research, they found each other -- and this project -- because they happened to land lab space next to one other at Norris Cotton. "Both of us are doing cancer work because of the cancer center," Fiering says. "There’s gravity in the cancer center that captures orbiting scientists. It’s real."
The big mystery that they're trying to solve is how the protein -- known for short as PLVAP and first identified by Stan -- actually works. To understand where they're headed, you need to know that the immune system basically relies on two arms: one that ramps it up (known as an immune-effector response) and one that tamps it down, or suppresses it. Tumors somehow manage to suppress the immune response.
A PLVAP-made endothelial diaphragm exhibiting a cartwheel architecture similar to “roman windows." Photo credit: John Heuser
"Tumors are actually recognized as a problem by the immune system," says Fiering. "But they recruit immuno-suppressive cells that protect them from the immune system. In other words, the system recognizes them, goes to attack, and then meets all these cells that give it 'Stand Down, Shut Up, and Be Quiet' signals."
When Stan and Fiering remove the protein, however, immune cells that fight tumors become effective. In other words, with the protein gone, says Stan, "the immune system gets activated to kill the tumor better."
The question, of course, is how. And that's what their $25,000 Prouty grant is funding: research into just what's going on. The two are cautious about drawing any grand conclusions. "I'm not sure that it's useful to go much further than, 'We don't understand the mechanism,'" says Stan. "We got the funding to try to solve the mystery."