Clear targets
In attacking the "molecular underpinnings" of pancreatic cancer, as Mayer puts, researchers have at least two goals in mind. One is to identify and map the complex network of abnormal genes and growth signals that drive tumors. Then the scientists, working with pharmaceutical companies, could design drugs or combinations of them to counteract the malignant growth signals present only in tumor cells. As with the leukemia drug Gleevec®, pancreatic cancer might be halted or controlled, even if the tumor didn't disappear.
Goal number two is to make early detection possible by discovering "biomarkers" — proteins or other substances made by the tumor or pancreas early in the disease — which could be detected by a blood test or other simple screening method. Unlike breast cancer, which can be identified by mammograms while curable, or colon cancer, where harmless polyps can be removed before they become cancerous, there's currently no way to screen for pancreatic cancer.
"Real progress is going to come with a better understanding of the molecular underpinnings of pancreatic cancer."
—Robert Meyer, MD
Nabeel Bardeesy, PhD, who led the successful effort in DePinho's lab to make experimental mice with mutated genes that resulted in aggressive pancreatic cancer, is using the animal model to learn more about how these abnormal genes work in people. After they discover mutations in samples of human pancreatic tumors, Bardeesy and his colleagues can breed mice containing combinations of these genes.
"Then we can disrupt these gene pathways and see what happens to the tumor, demonstrating whether these pathways are good targets for drugs," he says. Those experiments are currently under way at the Institute.
Toward the second goal of searching for early detection markers, Bardeesy notes, researchers can breed mice that are genetically identical and raised in uniform environments. This makes it easier to design experiments in which scientists would repeatedly test the blood and urine of cancer-prone and normal mice, watching for substances appearing only in those with pancreatic cancer — and at a time when the tumor is small or just forming.
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