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Drug Development Series: Review

Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer

Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland

Requests for reprints: Manuel Hidalgo, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Room 1M88, 1650 Orleans Street, Baltimore, MD 21231-1000. Phone: 410-502-3850; Fax: 410-614-9006. E-mail: mhidalg1{at}jhmi.edu

Abstract

The rapidly expanding knowledge of the pathogenesis of pancreatic cancer at the molecular level is providing new targets for disease characterization, early diagnosis, and drug discovery and development. Gene mutation analysis has provided insight on the pathogenesis and progression from preinvasive lesions to invasive cancer. Gene and protein expression profiling has advanced our understanding of pancreatic ductal adenocarcinoma identifying genes that are highly expressed in pancreatic cancers, providing more insight into the clinicopathologic features of pancreatic cancer, and revealing novel features related to the process of tissue invasion by these tumors. The increasing knowledge of the pathway activation profile in pancreatic cancer is yielding new targets but also new markers to select patients and guide and predict therapy efficacy. The discovery of genetic factors of which the presence predisposes pancreatic cancer to successful targeting, such as the association of BRCA2/Fanconi anemia genes defects and sensitivity to mitomycin C, will eventually lead to a more individualized treatment approach. In summary, several decades of intensive research have originated multiple factors or biomarkers that are likely to be helpful in the diagnosis, characterization, and therapy selection of pancreatic cancer patients. A deep understanding of the relative relevance of each biomarker will be key to efficiently diagnose this disease and direct our patients towards the drugs more likely to be of benefit based on their particular profile. The development of new preclinical models is of paramount importance to achieve these goals. [Mol Cancer Ther 2006;5(4):787–96]

¹ Rubio-Viqueira et al., in press.

Received 1/ 4/06; revised 2/ 6/06; accepted 2/21/06.