Tyrosine kinase inhibitor acquired resistance mechanism alternates between EGFR and ALK in a lung adenocarcinoma patient

Drive gene mutation positive non‐small cell lung cancer achieves reliable clinical responses to subsequent target therapy. However, most patients will inevitably develop disease progression with multiple treatment failure. Next generation sequencing can identify clear resistance mechanisms. We report a case of a late stage, non‐smoking, male non‐small cell lung cancer patient that developed dual mutations and our attempts to determine the novel resistance mechanism. After systematic chemotherapy, he was administered multiple target therapy according to different genotypes. Larger panel gene detection was adapted after the failure of different treatments to investigate the resistance mechanism. Re‐biopsy and large panel NGS revealed an EGFR mutant lung adenocarcinoma with alternating changes in acquired resistance between EGFR and ALK. The total survival time was 73 months. The genotypes and treatments in this patient provide new insight of target therapy resistance mechanisms. Re‐biopsy and large panel gene detection should be performed for each driver gene mutation to provide precision treatment strategies.