The role of BIM gene deletion in ALK-mutated Non-small cell lung cancer treated with alectinib

Abstract

Alectinib, as a first-line therapeutic option for advanced ALK mutation-positive non-small-cell lung cancer (NSCLC), is now widely used in the clinic. However, the associated mechanisms of resistance are unknown. The first documented case of ALK-mutated NSCLC’s resistance to alectinib is herein reported in relation to BIM gene deletion status. In particular, cell inhibition assay (CCK8 assay), cell transfection, fluorescence microscopy, RT-PCR, cell proliferation assay, cell migration assay and western blotting were undertaken for exploring the link between BIM status and alectinib resistance. Clinical cases showed that the BIM gene was absent in alectinib-resistant tumor tissues. Further experimental validation yielded that NSCLC with deleted BIM genes were less sensitive to aleitinib. BIM gene deletion can increase resistance to alectinib, and the potential efficacy of a combination of BIM sensitizer and alectinib to overcome alectinib resistance can be explored.