Clinical Characteristics and Spatial transcriptome analysis of Early Resistance to Alectinib in ALK-Positive non-small cell lung cancer: A Retrospective OLCSG Study

In anaplastic lymphoma kinase (ALK) gene rearrangements positive lung cancer, alectinib has shown good efficacy and is used as a first-line drug. However, some cases show early resistance within 3 months, but the characteristics of these cases have not been established. We analyzed patients with unresectable stage III/IV without indications for radical radiotherapy and recurrent ALK-positive lung cancer who received alectinib for primary ALK-TKI. Spatial transcriptome analysis and immunohistochemical staining revealed upregulation of Annexin A1 (ANXA1) in the early resistant group. Overall design: Six cases with surgically resected samples were analyzed using the NanoString GeoMx instrument. Two patients were in the early resistant group and four were in the responder group. 34 ROIs were selected that were representative of each tumor. Immunofluorescence staining was performed using PanCK, CD45, CD68, and SYTO13. We separately profiled RNA from tumor areas (PanCK+). ANXA1, LCN2, and CLDN4 were upregulated in tumor areas with the early resistance group.