A story of ALK variants and the efficacy of ALK inhibitors: moving toward precision oncology

In the era of precision medicine, rearrangement of the anaplastic lymphoma kinase (ALK ) gene has been proven to be a targetable oncogenic driver in 3–7% of patients with advanced non-small cell lung cancer (NSCLC) (1). Multiple clinical trials have demonstrated the superiority of ALK inhibitors compared with chemotherapy for treating patients with ALK-rearranged NSCLC; however, the responses to ALK inhibitors have varied in each study (2-7). Fluorescence in situ hybridization (FISH) or VENTANA anti-ALK (D5F3) immunohistochemistry, which are widely used as standard tests for ALK detection for enrollment in clinical trials, are unable to distinguish between the different variants or fusion partners of the ALK gene. The impact of ALK variants on the heterogeneity of the response to ALK inhibitors has not been fully elucidated.