| Description |
Background: In the United States more than 46,000 people will be diagnosed with pancreatic cancer. Although it is relatively rare, pancreatic cancer is the 4th leading cause of cancer death in men and women. Gemcitabine, the most common treatment for pancreatic cancer has less than 10% partial response rate. Also, Gemcitabine resistance is common in pancreatic cancer patients. Therefore, there is a clinical need to improve outcomes for patients diagnosed with pancrease cancer. Many cancers, including pancreas cancer, overexpress Axl, a receptor tyrosing kinase, which may provide a survival advantage for the cancer cells. Methods: A pancreatic adenocarcinoma tumor was obtained from patient undergoing a resection at the Huntsman Cancer Institute and was propagated as subcutaneous tumors in female SHO immunocompromised mice (IRB and IACUC approved]. The expanded tumor was then implanted orthotopically nto the pancreas of 40 SHO female mince. Two weeks later, after the tumor had established, the mice were randomly assigned to the following treatment groups: 1] control; 2] gemcitabine + abraxane; 3] Axl inhibitor low dose; and 4] Axl inhibitor high dose. The mice were treated for 4 weeks and then sacrificed. At harvest the primary tumor was weighed and areas of metastasis were identified. Results: The gemcitabine abraxane group [0.03+0.02g] had statistically smaller tumors than the control group [2.0+1.6g], Axl Low [1.1+o.7%g], and Axl High [1.2+1.0g][p=0.008]. The gemcitabine abraxane group [0%] also had a lower incidence of metastasis than the control [70%], Axl Low [30%], and Axl High [40%] groups [p=0.04]. Discussion: The greatest efficacy was observed in the tumors treated with gemcitabine abraxane. However, there was an inhibitory effect of treatment with the Axl inhibitor on both primary tumor growth and metastasis. Further studies are needed to determine if the efficacy of treating with an Axl inhibitor could be improved with a combination treatment approach, such as an Axl inhibitor along with gemcitabine or abraxane. |
