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
Division of Pulmonology, Centre Hospitalier Universitaire de l'Université Catholique de Louvain (CHU UCL) Namur (Godinne Site), Université Catholique de Louvain, Yvoir, Belgium.
Respiratory Oncology Unit (Pulmonology), University Hospitals Katholieke Universiteit Leuven, Leuven, Belgium.
Front Oncol. 2022 Nov 7;12:985446. doi: 10.3389/fonc.2022.985446. eCollection 2022.
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 -rearranged lung adenocarcinoma who developed a 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 A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of mutation in NSCLC, and A598-T599insV mutation in other cancers.
间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKIs）改善了晚期ALK重排非小细胞肺癌（NSCLC）的预后，但耐药机制限制了它们的疗效。我们描述了一名63岁的cIVA期ALK重排肺腺癌男性患者的病例，该患者发生了A598-T599insV突变，这是对第二代ALK TKI阿来替尼的一种潜在耐药机制。他接受了BRAF和MEK抑制剂联合治疗，但在治疗开始两个月后，因肿瘤进展和毒性反应而死亡。基于肺癌中首次报道的A598-T599insV突变，我们讨论了ALK TKIs的耐药机制、该突变在NSCLC中的意义以及A598-T599insV突变在其他癌症中的情况。
