Molecular and morphologic study of pancreatic cancer evolution

Abstract

Pancreatic cancer has a dismal prognosis. We have studied this cancer through the eyes of Charles Darwin: with the focus on how these tumors arise and evolve. With molecular techniques and analyses from evolution theory, we have definitively shown how cysts in the pancreas can result in pancreatic cancer. We also describe that when these cystic precursor lesions start to invade into the surrounding tissue, this is associated with mutations in the SMAD4 and TGFBR2. In addition, we studied the three-dimensional morphology of this cancer through tissue clearing techniques. We found that pancreatic cancer has multiple mechanisms of invasion in the surrounding tissue and that the cancerous cells often grow next to veins. This explains why pancreatic cancer has such a bad prognosis and why these tumors metastasize in a very early stage to the liver: because the pancreatic veins drain the blood from the pancreas to the liver and they can take easily take cancer cells with them.