Johns Hopkins Magazine

Johns Hopkins Magazine

Detecting a Cure - In the war against cancer, molecular biomarkers hold out tantalizing promise.
In January 2003, Levy traveled from his home in Cherry Hill, New Jersey, to Hopkins for the initial screening, which included a consultation with a geneticist, blood testing, and endoscopic ultrasonography (EUS). The geneticist recommended that Levy be tested for mutations in the BRCA genes, which were originally associated with breast cancer and now are also associated with pancreatic cancer. As an Ashkenazi Jew (of Eastern European descent), Levy was much more likely to have this mutation. Gastroenterologist Marcia Canto conducted the EUS, and she found a subtle abnormality. "I was surprised," Levy says. "My attitude when I went into this study was, they want to collect data and I'll have the opportunity to get some sophisticated imaging. I didn't think it would show anything, but I had nothing to lose."
Canto ordered an ERCP (endoscopic retrograde cholangiopancreatography), in which a catheter goes into the pancreatic ducts and injects dye so that an X-ray can be taken, and a multi-detector CT scan. The lesion appeared to be chronic pancreatitis, not anything to be happy about, but not cancer, either. But at a follow-up test in January 2004, Canto concluded that the lesion was intraductal papillary mucinous neoplasm (IPMN), or pre-cancerous cells — and that it appeared to be progressing. In the meantime, another warning sign had come in: the results of Levy's genetic tests. He had a BRCA2 mutation.
Doctors recommended a Whipple resection, surgery that removes the head of the pancreas, where Levy's lesion was located, as well as a portion of the small intestine, common bile duct, and gall bladder. The Whipple procedure is major surgery and requires weeks for recovery. But IPMNs are thought inevitably to become invasive cancer — and the lesion was already at 1 centimeter. Levy remembered his uncle and father, and made his decision.
While he was in Johns Hopkins Hospital, Levy met three other men also having the Whipple. These men had actual pancreatic cancer. The same surgery Levy was choosing gives people with full-blown pancreatic cancer their only real hope: overall, a 20 percent chance of survival. "They were way worse off than me," Levy says. "I was going through it just as an elective procedure."
Six days after the surgery, Ted Levy walked out of the hospital, a little sore but cancer-free. For the time being, at least, he has stopped the disease dead in its tracks. "Early detection of that IPMN using clinical screening probably cured him," says Michael Goggins, director of the Johns Hopkins Pancreatic Cancer Early Detection Laboratory, who designed the CAPS studies with Canto. "This is really going after cancer."
As fortunate as Levy was, imaging is only one side of the new diagnostic coin. Often, doctors cannot discern from imaging alone if an abnormality is cancer. In an earlier CAPS study, subjects also underwent imaging of their pancreas. Two patients who went to surgery with subtle imaging abnormalities did not have a tumor. This is why the new molecular tests are so necessary: to know whether a patient has cancer and thus needs surgery in the first place. And it's why the CAPS2 researchers now also collect blood and pancreatic fluid from patients to find a common molecular biomarker among those who turn out to have the disease. Goggins' group has identified a number of markers that can be identified in the blood and in pancreatic fluid. The tests they are working on will help best decide who needs surgery and who does not. Molecular tests like this are in the works for many different kinds of cancers all over the scientific world, and especially at Johns Hopkins.
One of these tests is already on the market and being used in a clinical setting. PreGen-Plus", a stool-based DNA test that detects colon cancer, was released in August 2003. Developed by EXACT Sciences, it is the first cancer test available that uses biomarkers to screen for the presence of actual cancer.