Pancreatic Cancer Case Study

Pancreatic cancer (PaCa) is a rapidly progressive and metastatic cancer with the lowest survival of any human cancer. Resistance of PaCa to current treatment regimens contributes to the dismal prognosis of this malignancy. There have been over ten phase II/III clinical trials aiming at curing PaCa during the past decade without significant success. In fact, a recent trial showing that Abraxane when combined with gemcitabine improved the overall patient survival by 1.8 months compared to gemcitabine alone was considered a success despite marginal benefits. Of particular importance, military personnel and military veterans are at significantly greater risk for pancreatic cancer compared to the general population likely due to greater environmental exposures to risk factors know to be associated with this cancer.
We have made key advances that are directly applicable to treating this disease in a more effective way that can result in prolonging life in patients who contract pancreatic cancer.
One is that we have developed a method to isolate and grow cancer cells that are circulating in the blood both in culture and in experimental animals. This is an extremely important advance because we demonstrated the cells from the PaCa patient that are circulating in the blood are able to spread and create metastases in other organs. The spreading and metastases are the factors that result in death from the cancer. We propose to study the cancer cells circulating the blood to find out if they are different in different stages of the cancer and if there are markers or identifiers on different groups of the circulating cancer cells. Having ways to identify different types of circulating cancer cells between patients, from the same patient and with different phases of the disease will provide us a way to develop improved treatments at individualized
basis.
The other major advance is that we have developed two new drugs specifically to delay the spreading and eradicate previously metastasizing pancreatic cancer that is resistant to current medications. In one, we developed a method that carries a currently used drug, gemcitabine, directly into the cancer cell and not normal cells, by conjugating gemcitabine chemically with a new drug carrier. The other drug we have developed was designed to specifically inhibit biochemical pathways in cancer cells that give them the ability to spread and metastasize. We provide animal testing data that is showing the benefit of these agents and submitted patents in support of our findings in this application.
Using these new drugs in combination with our unique ability to grow and test the drugs against these cells that are responsible for the deadly nature of the disease will provide better treatments and prolongation of life for patients with pancreatic cancer. Furthermore, by finding markers in these circulating cancer cells that distinguish between the different types of circulating cancer cells and associating the markers with a better response to one of our new drugs will provide a unique opportunity to choose treatments individualized to the patient.
We are an interactive group from three medical centers with the complementary and necessary skills required to achieve the goals of the proposal. Furthermore, at the same time we are performing the studies described in this proposal, we will be performing safety studies so that, at the end of the study period, we will be able to proceed with clinical trials. Thus, clinical trials of our combined typing of circulating cancer cells and the new drugs will start in approximately 4 years. The proposed research project will thus be benefiting military personnel and veterans, their families and as the general public.