Case Report: Successful late-line pralsetinib treatment in an ALK-rearranged lung adenocarcinoma patient with KIF5B-RET fusion resistant to alectinib

Anaplastic lymphoma kinase (ALK) fusion, an oncogenic driver alteration, accounts for 5%–6% of non-small cell lung cancer (NSCLC) patients. ALK tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in advanced ALK-rearranged NSCLC. However, acquired resistance to ALK TKIs inevitably...

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Bibliographic Details
Main Authors: Feng Jin, Chenyang Wang, Fang Yang, Shubin Wang, Fen Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1569912/full
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Summary:Anaplastic lymphoma kinase (ALK) fusion, an oncogenic driver alteration, accounts for 5%–6% of non-small cell lung cancer (NSCLC) patients. ALK tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in advanced ALK-rearranged NSCLC. However, acquired resistance to ALK TKIs inevitably arises, and the underlying mechanisms remain incompletely elucidated. This report describes a stage IV lung adenocarcinoma (LUAD) patient with ALK-rearranged who developed KIF5B-RET fusion-mediated resistance following second-line alectinib therapy. The patient achieved a partial response (PR) to third-line pralsetinib, sustained for 4 months. This case highlights KIF5B-RET fusion as a potential resistance mechanism post alectinib treatment and suggested = pralsetinib, a RET inhibitor, as a viable therapeutic option in this context. These findings contribute to the evolving understanding of resistance management strategies in ALK-rearranged NSCLC.
ISSN:1664-8021