Analysis of bypass signaling in EGFR pathway and profiling of bypass genes for predicting response to anticancer EGFR tyrosine kinase inhibitors

摘要: Some drugs, such as anticancer EGFR tyrosine kinase inhibitors, elicit markedly different clinical response rates due to differences in drug bypass signaling well genetic variations of target and downstream drug-resistant genes. The profiles these are expected be useful for improved prediction, which have not been systematically explored previously. In this work, we searched analyzed 16 literature-reported inhibitor routes the pathway, include 5 compensatory transactivation by another receptor, 11 alternative activated receptor. These reportedly regulated Their expression together with mutational, amplification 4 genes, were used new sets biomarkers identifying 53 NSCLC cell-lines sensitive or resistant inhibitors gefitinib, erlotinib lapatinib. collective all genes distinguish better than those individual combined their derived cell-line consistent reported three drugs. usefulness data studies was further comparing patient samples, using a machine learning feature selection method selecting biomarkers. Our study suggested that highly prediction.