AUTHOR=Jin Feng , Wang Chenyang , Yang Fang , Wang Shubin , Wang Fen 

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2025.1569912

DOI=10.3389/fgene.2025.1569912

ISSN=1664-8021

ABSTRACT=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.