The AACR-FNAB Fellows Grant for Translational Pancreatic Cancer Research provides funding to allow a meritorious young investigator to pursue an independent line of investigation within the context of his/her current fellowship placement. This grant provides a “bridge” between a training and an independent position, offering an opportunity for a young investigator to develop a new direction for his/her research program that otherwise may not have been possible in the absence of this funding.
Olorunseun O. Ogunwobi, M.D., Ph.D.
Postdoctoral Fellow, University of Florida College of Medicine, Gainesville, FL
Mechanisms of Metastasis in Pancreatic Cancer
“Metastasis is the greatest cause of mortality due to cancer. Unfortunately, whilst significant progress has been made in understanding the etiology and progression of many primary cancers, the basis for metastases of cancers generally remains largely unclear. A number of biological concepts have been proposed as potential role-players in cancer metastasis. Two of these are: epithelial-mesenchymal transition (EMT) and the concept of cancer stem cells. Although many in vitro and animal studies have provided some experimental support for these ideas, no human study to date has provided definitive support for these concepts. Moreover, data from some recent animal studies have questioned the usefulness of these concepts in explaining cancer metastasis. It is, therefore, necessary to explore other possible explanations for cancer metastasis. Although research has focused on the biology of cancer cells from the primary tumor and cancer cells from metastatic lesions and there is some data suggesting that circulating cancer cells have increased metastatic potential, nobody knows what actually happens to cancer cells once they escape from their primary site that enables some of them to survive in the immunologically hostile environment in blood and acquire the capability to colonize secondary sites and become metastatic lesions. I hypothesize that viable cancer cells able to circulate in the blood of cancer patients possess important molecular differences from cancer cells at the primary site of tumor and that targeting these differences may be a potentially effective approach to preventing or treating cancer metastasis. To explore this innovative and novel approach to the study of cancer metastasis, I will use pancreatic cancer as a model. Pancreatic cancer is known to be a metastatic disease with extremely high mortality rate of up to 98 percent. The primary lesion is in the pancreas, but patients may develop metastasis to the liver, lungs, brain, etc. Pancreatic cancer is the fourth highest cause of deaths due to cancers here in the United States. I will focus on isolating, culturing and performing detailed molecular and functional characterization of cancer cells from blood of pancreatic cancer patients because distant metastases is believed to occur almost entirely via hematogenous spread. The effects of molecularly targeted therapies on the CCCs will then be directly examined to determine the most appropriate personalized cancer management for each patient with pancreatic cancer.”