biostudies-literatureUnknown13Zhao JThe effectiveness of the tyrosine kinase inhibitor ALK (TKI) for non-small cell lung cancer has been confirmed. However, resistance to ALK-TKIs seems inevitable. Mutations in the ALK kinase domain have been reported as an important mechanism of acquired resistance to ALK therapy. However, patients with <i>de novo</i> ALK kinase domain mutations and ALK rearrangements who were not treated with ALK inhibitors have rarely been reported. Here, we report a case of primary drug resistance to first- and second-generation ALK inhibitors in a NSCLC patient with ALK-rearrangement. The next-generation sequencing test of the pathological biopsy showed that the <i>de novo</i> ALK kinase domain mutation F1174L-cis-S1189C may be the cause of primary drug resistance.Frontiers in pharmacology1060460https://www.ebi.ac.uk/biostudies/studies/S-EPMC9727108biostudies-literaturePrimary resistance to first- and second-generation ALK inhibitors in a non-small cell lung cancer patient with coexisting ALK rearrangement and an ALK F1174L-cis-S1189C <i>de novo</i> mutation: A case report.PMC9727108Liu HWang BGuo YLiang YQin YFan RLi XGuan YLi SFan JZhang XZhao JWang ZWu XfalsePrimary resistance to first- and second-generation ALK inhibitors in a non-small cell lung cancer patient with coexisting ALK rearrangement and an ALK F1174L-cis-S1189C <i>de novo</i> mutation: A case report.The effectiveness of the tyrosine kinase inhibitor ALK (TKI) for non-small cell lung cancer has been confirmed. However, resistance to ALK-TKIs seems inevitable. Mutations in the ALK kinase domain have been reported as an important mechanism of acquired resistance to ALK therapy. However, patients with <i>de novo</i> ALK kinase domain mutations and ALK rearrangements who were not treated with ALK inhibitors have rarely been reported. Here, we report a case of primary drug resistance to first- and second-generation ALK inhibitors in a NSCLC patient with ALK-rearrangement. The next-generation sequencing test of the pathological biopsy showed that the <i>de novo</i> ALK kinase domain mutation F1174L-cis-S1189C may be the cause of primary drug resistance.2022-01-01T00:00:00Z20222026-04-08T11:31:46.434Z2024-11-07T10:22:30.326ZS-EPMC97271083650653910.3389/fphar.2022.1060460