ReviewCellular and molecular aspects of pancreatic cancer
Section snippets
History
It was believed for a long time that cancer of the pancreas was not existent, and it was not until 1882 when a solid tumor was successfully excised for the first time from this tissue. The patient, however, died within hours of being discharged (Busnardo et al., 1983). Since then, many surgical procedures have been proposed for resection of malignant pancreatic tissue. Walter Kausch and Allan Whipple started performing pancreatic surgery around 1910 and developed a method known as
Factors contributing to poor survival
There are several reasons why PDAC patients have such low survival. First, there are few viable methods for detecting this malignancy early. Second, PDAC is a highly aggressive cancer and can metastasize early. Finally, few targeted therapies exist for treating PDAC, and those therapies that are used remain relatively ineffective.
Genetically engineered mouse models (GEMMs)
Genetically engineered mouse models (GEMMs) for PDAC research were created to recapitulate both genetic and morphologic alterations that often lead to the development of the disease. Experiments conducted in mouse models have shown identical results to human PDAC. Over the past decade, pancreatic cancer GEMMs have garnered significant attention since they show promise for assisting in the development of new diagnostic and therapeutic approaches. Here, we discuss genes alterations that have been
Oncogene addiction
Cancer cells often times depend on specific oncogenes for their growth and survival. This concept is known as “oncogene addiction” (Weinstein and Joe, 2008). Targeting a single oncogene that drives tumor cell survival would be the most ideal approach for defeating malignancies; however, there has been little success with this approach. Because these tumor cells are exceedingly reliant on specific oncogenes, it has been predicted that these genes or cells carry second-site mutations prior to
Proteomics
Over the past decade, proteomics has quickly found its place as a useful technique for identifying potential biomarkers or therapeutic targets since this method can detect the protein and post-translationally modified protein levels (Anderson and Anderson, 1998). Identification of such biomolecules may help in predict disease prognosis and identification of new targets; thus, in the case of PDAC, proteomics is very practical. One application of this method is to compare normal and tumor tissue
Concluding remarks
Research on pancreatic cancer has vastly increased over the past few decades, yet the survival rate has remained rather low. Advancements in technologies have provided us a “blue-print” of PDAC initiation, development and progression. This has given us the opportunity to identify potential biomarkers and therapeutic targets for this malignancy; however, more studies are required for definitive treatment options. Due to the lack of noticeable symptoms while the tumor is localized to the
Acknowledgements
We thank the members of the Kelber Lab at California State University Northridge. Funding that supported this and related work came from the CSUN College of Science and Math, Medtronic/Minimed, CSUPERB and the Sidney Stern Memorial Trust.
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