Molecular Characterization of Pancreatic Cancer Cell Lines
A Relatively large number of very well characterized human pancreatic cancer cell lines is available for preclinical investigation. However, there is a perception that continuous passage in tissue culture coupled with genomic instability has made them poo
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Introduction: Preclinical Models of Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
2 Common Assumptions About Established Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 2.1 ‘‘Cell Lines Are Genetically Scrambled’’ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 459 2.2 ‘‘The Effects of Drugs on Cancer Cells in Tissue Culture Cannot Predict their Activities in Patients’’ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460 2.3 ‘‘Effects of Drugs in Two Dimensional Growth Conditions Have No Relationship to Their Effects in 3D and/or In Vivo’’ . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461 3
Heterogeneity in Human Pancreatic Cancer Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . 462
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Characteristics of Orthotopic Xenografts Derived from Established Cell Lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
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Summary and Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
J. P. Neoptolemos, R. Urrutia, J. L. Abbruzzese, M. W. Bu¨chler (eds.), Pancreatic Cancer, DOI 10.1007/978-0-387-77498-5_19, # Springer Science+Business Media, LLC 2010
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Molecular Characterization of Pancreatic Cancer Cell Lines
Abstract: A Relatively large number of very well characterized human pancreatic cancer cell lines is available for preclinical investigation. However, there is a perception that continuous passage in tissue culture coupled with genomic instability has made them poor models of human disease and that preclinical attempts to identify active therapeutic regimens that employed them as models have uniformly failed when they were translated into clinical trials. Here we will review the current status of some high profile studies employing cell lines to model human cancer biology and identify the potential strengths and weaknesses associated with the approach. We will also discuss results that challenge the notion that cell lines are poor models of human cancer biology.
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Introduction: Preclinical Models of Pancreatic Cancer
Pancreatic cancer is a uniformly lethal disease, and identifying new approaches for early detection and therapeutic intervention are exceptionally high priorities in cancer research. Fortunately, even though less funding has been allocated to the study of pancreatic cancer than to other types of cancer, a relative wealth of preclinical models are available to researchers in the field. They can be grouped broadly into three categories: established human cell lines (and xenografts derived from them), transgenic mice, and ‘‘tumorgrafts’’ (also known as ‘‘primary human xenografts’’). All are being used to better understand the biology of human disease and to develop biology-based therapies that will be more effective than the current standard of ca
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