Pancreatic cancer is the fourth leading cause of death related to cancer in the United States and results in approximately 30,000 deaths each year. Currently there are no effective chemotherapeudic treatments for pancreatic cancer and the five year survival rate is less than 5%. It is clear that research needs to be directed toward developing new drugs to treat this deadly disease. Novel taxane derivatives have been shown to have anti-tumor activity in a xenograft model of colon and ovarian cancer. These taxane derivatives are particularly promising in light of their ability to overcome multidrug resistance, a factor that has compromised the effectiveness of the original taxane compounds. Multidrug resistance is particularly relevant as pancreatic cancer is refractive to conventional therapy because of the expression of multidrug resistance proteins. In this study taxane derivatives were shown to stop the growth of pancreatic cancer cells in vitro. Two taxane derivatives were tested on 4 pancreatic cancer cell lines and were shown to have an IC 50 that ranged between 1-10nM. The efficacy of the compounds did not appear to be affected by the expression of multidrug resistance proteins. The compounds were also tested in a xenograft model of human pancreatic cancer and were shown to significantly reduce tumor burden in animals bearing multidrug resistant pancreatic cancer cells. Ultimately this project will form the basis for future clinical trials in patients that have pancreatic cancer.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]