In a series of experiments to determine the likely mechanism of this resistance, exome sequencing revealed an increased copy number for the gene encoding wild type Kras in one line of crizotinib resistant cells and in a study of tumour biopsies taken from patients with acquired resistance to TKI therapy 3 out of 15 patients (20%) had focal amplification of Kras indicating that this is a bona fide resistance mechanism to ALK-specific TKIs in lung adenocarcinoma. Here, KRAS is linked to lung adenocarcinoma.