AUTHOR=Pasau Thomas , Wauters Els , Wauters Isabelle , Duplaquet Fabrice , Pirard Lionel , Pop-Stanciu Claudia , D’Haene Nicky , Dupont Michael , Vander Borght Thierry , Rondelet Benoît , Ocak Sebahat 

TITLE=Case report: BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib in ALK-rearranged lung adenocarcinoma

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.985446

DOI=10.3389/fonc.2022.985446

ISSN=2234-943X

ABSTRACT=<p>Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA <italic>ALK</italic>-rearranged lung adenocarcinoma who developed a <italic>BRAF</italic> A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of <italic>BRAF</italic> A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of <italic>BRAF</italic> mutation in NSCLC, and <italic>BRAF</italic> A598-T599insV mutation in other cancers.</p>