Blockade of AXL activation overcomes acquired resistance to EGFR tyrosine kinase inhibition in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for ~85% of the cases (1,2). Activating epidermal growth factor receptor (EGFR) mutations, most commonly exon 19 deletions and the L858R mutation of exon 21 can be identified in 10–35% NSCLC patients and have been shown to play a driver oncogenic role in malignant transformation and progression (1-5). EGFR mutations are usually heterozygous, with the mutant allele also commonly showing gene amplification (4,5). These mutations increase constitutive activation of the receptor without ligand binding, leading to hyperactivation of downstream pro-survival signaling pathways (4,5). The over-activation of growth-promoting signaling is associated with tumor progression and metastasis