While consideration should be given to the individual capabilities of diagnostic laboratories, the testing selleck inhibitor of these additional samples may lead to an increase in the number of successful mutation results, enabling a greater number of patients to be accurately diagnosed, and receive the most effective and personalized therapy. This work was supported by AstraZeneca, UK. J.C.-H. Yang has received advisory fees from AstraZeneca, Roche, Genentech, Pfizer, and Clovis, and has been an uncompensated advisor to Boehringer Ingelheim and Eli Lilly. Y.-L. Wu and K. Nakagawa have received speaker fees from
AstraZeneca. G. McWalter and R. McCormack are employees of AstraZeneca and hold shares in AstraZeneca. T.S. Mok has received research funding from AstraZeneca and advisory fees from AstraZeneca, Roche, Eli Lilly, Boehringer Ingelheim, Merck Serono, and Pfizer. M. Fukuoka, N. Saijo, V. Chan, and J. Kurnianda have no conflicts of Dasatinib in vitro interest to disclose. The authors would like to thank the patients and investigators for their participation in the IPASS study. Sample analysis
was performed by Dr Guanshan Zhu, Dr Li Zheng, and Dr Peter Lu at Innovation Center China (China cohort) and Genzyme genetics (non-China samples). Statistical analysis was performed by Dr Rosie Taylor from AstraZeneca, UK. Editing support funded by AstraZeneca was provided by Sarah Lewis, from Complete Medical Communications. “
“Non-small cell lung cancer (NSCLC) is the most common
type of lung cancer, accounting for approximately 80% of lung cancers. NSCLC is attributed in part to somatic mutations of the epidermal growth factor receptor gene (EGFR) [1]. The most common mutations are an in-frame E746-A750 deletion in exon 19 and a single-point substitutional L858R mutation in exon 21, both of which are located in the tyrosine kinase domain of EGFR. These two mutations are observed in approximately 90% of EGFR mutations and are termed “activating mutations” [2]. EGFR-TKIs, such as gefitinib and erlotinib, block autophosphorylation of EGFR with subsequent inhibition of the downstream signaling Cediranib (AZD2171) pathways involving RAS/extracellular signal regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K)/AKT, and show favorable activity in NSCLC patients with activating mutations of EGFR [3]. However, almost all patients eventually develop acquired resistance to EGFR-TKIs within several years [4]. Two genetic mechanisms of acquired resistance to EGFR-TKIs have been identified in EGFR-mutated NSCLC. A secondary mutation of T790M in exon 20 of EGFR and amplification of the MET oncogene are observed in approximately 50% and 5% of resistant cases, respectively [5], [6], [7] and [8]. Moreover, Yano et al. showed that overexpression of hepatocyte growth factor (HGF), a ligand for MET, induces acquired resistance by activating MET signals [9].