Mutation profiling of circulating tumor cells in ALK-rearranged NSCLC showed progressive intratumor heterogeneity and concomitant co-occurrence of mutations in ALK-independent pathways in acquired resistance to ALK-TKI22,23; thus, progression of tumor heterogeneity makes conquering drug resistance in ALK-rearranged NSCLC tumors difficult. This evidence concerns the gene ALK and non-small cell lung carcinoma.