Pancreatic cancer is resistant to standard surgical and non-selective antimetabolite therapy, with median survival of patients with resectable disease and adjuvant therapy remaining around 20 months and those with unresectable disease at <6 months with the most effective currently available therapy (1, 2). Innovations in genomics and proteomics have led to the identification of numerous potential targets for the development of novel antineoplastic agents and early detection biomarkers. This chapter looks at the history of targeted approaches to drug design, recent developments in the fields of genomics and proteomics, and the potential application of these approaches to pancreatic cancer treatment and early detection.
Molecular targeting by pharmaceuticals was made possible in the middle of the last century by the discovery of specific biochemical pathways. Early examples of targeted drugs included propranolol, allopurinol, and cimetidine. Black, Hutchings, and Elion received the Nobel Prize in 1988 for their work on developing these compounds ( 3, 4 ). Identification of similarly specific targets in cancer has noticeably lagged behind, with the exception of antimetabolites. Only recently have targeted therapies such as trastuzumab (anti-HER2 neu antibody effective against breast cancer) and imatinib mesylate (a BCR-ABL tyrosine kinase inhibitor for treatment of chronic myeloid leukemia and gastrointestinal stromal tumors) become available. For pancreatic cancer, bevacizumab (Avastin), a recombinant humanized antivascular endothelial growth factor (VEGF) monoclonal antibody, showed promising results in phase II trials ( 5 ), but was subsequently shown to provide no survival benefit ( 6 ). The push to identify specific molecular targets for the rational design of antineoplastics (in particular cancer cell signaling molecules and molecules that can affect the cancer cell microenvironment) has led to rapid development of techniques in genomics and proteomics. These techniques hold promise in identifying novel and effective targets for the treatment of pancreatic cancer.
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Heidt, D.G., Misek, D., Lubman, D.M., Simeone, D.M. (2008). Incorporation of Genomics and Proteomics in Drug and Biomarker Development. In: Lowy, A.M., Leach, S.D., Philip, P.A. (eds) Pancreatic Cancer. M. D. Anderson Solid Tumor Oncology Series. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-69252-4_43
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