Скачать или смотреть Antonio Baines - Oncoproteins K Ras and Pim kinases as molecular targets in pancreatic cancer

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Pancreatic cancer is the 4th most common cause of cancer deaths in the United States. Due to the aggressive nature of this cancer and the lack of biomarkers for early detection, the incidence and mortality rates for pancreatic cancer are nearly equivalent. The presence of oncogenically mutated K-Ras in 90% of human pancreatic ductal adenocarcinomas (PDAC) strongly suggests a critical role for this genetic mutation in the development of this disease. We and others demonstrate that mutated K-Ras can activate one or more downstream signaling pathways, including the RalGTPase pathway, and lead to transformed growth in PDAC. However, despite many years of research, there are no anti-Ras therapies that have successfully reached the clinic. One of the genes that have been found by microarrays to be overexpressed after oncogenic K-ras is Pim-1 kinase. Most recently, another member of the Pim family, Pim-3 kinase, was shown to be aberrantly expressed and to block apoptosis in PDAC cell lines and patient tumors. With these and other observations implicating Pim kinases as oncogenes and inhibitors of apoptosis, the overall goal of our research is to determine the functional significance of the Pim kinase family in PDAC growth. We hypothesize that inhibition of one or more Pims will be an effective approach for antagonizing the aberrant growth of pancreatic carcinoma. Our results will help to define the role of K-Ras activation in Pim upregulation and determine the consequences of Pim inhibition on PDAC growth. Furthermore, these findings will allow us to critically validate these kinases as novel therapeutic targets for PDAC treatment.
Learning objectives:
1. Discuss the importance of oncogenic K-Ras and downstream signaling pathways in the development and progression of pancreatic cancer.
2. Discuss the roles of oncogenic Pim kinases in pancreatic cancer growth and as a potential drug target.