Acquired L858R mutation following -TKI resistance in lung adenocarcinoma: a case report.

Reports of secondary mutations in mutual exclusive driver genes after resistance to targeted therapy are rare. We present a patient with Anaplastic lymphoma kinase () fusion lung adenocarcinoma who received sequential treatment with ALK tyrosine kinase inhibitor (TKI) (crizotinib, PFS:32.3 months and then conteltinib, PFS: 29 months). Upon further disease progression, a lung biopsy and next-generation sequencing (NGS) revealed acquired secondary driver mutations including Epidermal Growth Factor Receptor ( L858R and mutation of F1174L. Subsequently, the patient switched to third generation -TKI treatment with almonertinib. This case suggests mutation is one of the mechanisms of -TKI resistance, highlights the value of re-biopsy in identifying potentially targetable resistance mechanisms and underscores the spatiotemporal heterogeneity of tumors under the selective pressure of -TKI.