Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer

Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer.     

A rough set approach to feature selection based on scatter search metaheuristic

Rough set theory is an effective method to feature selection, which has recently fascinated many researchers. The essence of rough set approach to feature selection is to find a subset of the original features. It is, however, an NP-hard problem finding a minimal subset of the features, and it is necessary to investigate effective and efficient heuristic algorithms. This paper presents a novel rough set approach to feature selection based on scatter search metaheuristic. The proposed method, called scatter search rough set attribute reduction （SSAR）, is illustrated by 13 well known datasets from UCI machine learning repository. The proposed heuristic strategy is compared with typical attribute reduction methods including genetic algorithm, ant colony, simulated annealing, and Tabu search. Computational results demonstrate that our algorithm can provide efficient solution to find a minimal subset of the features and show promising and competitive performance on the considered datasets.