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Target Discovery and Validation Reviews and Protocols

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<strong>Target</strong> <strong>Discovery</strong> <strong>and</strong> <strong>Validation</strong> in Pancreatic Cancer<br />

Robert M. Beaty, Mads Gronborg, Jonathan R. Pollack,<br />

<strong>and</strong> Anirban Maitra<br />

Summary<br />

Pancreatic cancer is a lethal disease <strong>and</strong> rational strategies for early detection <strong>and</strong> targeted<br />

therapies are urgently required to alleviate the dismal prognosis of this neoplasm. The use of<br />

global RNA <strong>and</strong> protein expression-profiling technologies, such as DNA microarrays, serial<br />

analysis of gene expression, <strong>and</strong> mass spectrometric analysis of proteins, have led to identification<br />

of cellular targets with considerable potential for clinical application <strong>and</strong> patient care. These<br />

studies underscore the importance of pursuing large-scale profiling of human cancers not only for<br />

furthering our underst<strong>and</strong>ing of the pathogenesis of these malignancies but also for developing<br />

strategies to improve patient outcomes.<br />

Key Words: Bioinformatics; DNA microarrays; pancreatic cancer; proteomics; target discovery;<br />

serial analysis of gene expression; SAGE.<br />

1. Introduction<br />

1.1. Pancreatic Cancer<br />

Infiltrating ductal adenocarcinoma of the pancreas, more commonly known as<br />

“pancreatic cancer” is the fourth leading cause of cancer deaths in the United<br />

States (1). It is estimated that in 2006, approx 213,000 individuals worldwide will<br />

be diagnosed with pancreatic cancer <strong>and</strong> approx 213,000 will die from this cancer<br />

(2). It is an almost uniformly fatal disease, with an overall 5-yr survival rate of less<br />

than 5%. The majority (~80%) of patients present with locally advanced or with<br />

metastatic malignancies, rendering the cancers surgically unresectable. Unfortunately,<br />

even patients who undergo surgical resection eventually succumb to<br />

metastatic disease, including those cases where the primary lesion was extremely<br />

small at diagnosis (3). The implication is that pancreatic cancer must metastasize<br />

distantly, before clinical presentation, in virtually all cases. A small number of<br />

From: Methods in Molecular Biology, vol. 360, <strong>Target</strong> <strong>Discovery</strong> <strong>and</strong> <strong>Validation</strong> <strong>Reviews</strong> <strong>and</strong> <strong>Protocols</strong><br />

Volume I, Emerging Strategies for <strong>Target</strong>s <strong>and</strong> Biomarker <strong>Discovery</strong><br />

Edited by: M. Sioud © Humana Press Inc., Totowa, NJ<br />

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