EGFR missense and deletion selleck bio mutations were found in 13.4% of non-small cell lung sellckchem Cancer (NSCLC) patients, within exons 18 through 21 of the kinase domain (4). Lynch et al. reported in-frame deletions and amino acid substitutions, clustered in the region of the ATP-binding pocket of the TK domain, in eight of nine patients with gefitinib-responsive NSCLC (5). While EGFR mutations are characteristic Inhibitors,research,lifescience,medical for NSCLC, PIK3CA mutations are also identified in glioblastomas, colorectal cancer, gastric cancer, and breast cancer (3,6). EGFR is expressed by many epithelial tumor cells, including biliary and pancreatic cancers (7-9). Inhibition of activated
protein kinases through the use of targeted small molecule drugs (i.e., Inhibitors,research,lifescience,medical gefitinib and erlotinib) or antibody-based (i.e., cetuximab and panitumumab) strategies have emerged as an effective approach to cancer therapy (10-12). EGFR expression itself is not a definite predictor of response to EGFR TK inhibitors (13), however, EGFR mutations in NSCLC were found to predict sensitivity to gefitinib (4). Phase II studies have shown that TK inhibitors (TKI) induced response in over 70% of NSCLC patients harboring EGFR mutations (14). Both pancreatic and biliary tract carcinoma Inhibitors,research,lifescience,medical are diagnosed at advanced stages when
incurable, Inhibitors,research,lifescience,medical and outcomes even with surgery and chemotherapy, are poor (15-19). Combination of erlotinib
and gemcitabine in advanced pancreatic cancer showed a modest increase in survival compared to gemcitabine alone, and resulted in the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) approval for this regimen as first-line treatment Inhibitors,research,lifescience,medical of pancreatic cancer (20). The objectives of this study were to determine the prevalence of EGFR and PI3K mutations in patients with pancreaticobiliary cancers. No studies had been reported at the time our research began of either EGFR or PIK3CA mutations in either disease. Several small reports have been published since, and this article will AV-951 summarize the current literature in this field. Materials and methods Study population This study was performed with approval of the Roswell Park Cancer Institute (RPCI) Institutional Review Board. The institutional pathology department reviewed all cases of pancreatic and biliary tract cancers following pancreatectomy diagnosed at RPCI over a period of five years between December 1, 1999, and November 30, 2004. All tumor blocks with adequate DNA for performing mutation analysis were selected for inclusion. Clinical data, including age, sex, ethnicity, and clinical stage, was obtained via chart review unblinded to mutation results. The samples were numbered consecutively to ensure patient confidentiality.