Wang Jian, Liu Bingyue, Zheng Qinhong, Xiao Ruoshui, Chen Jianxin
Department of Medical Oncology, International Ward, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China.
Jinhua Joint Training Base, The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China.
Front Oncol. 2024 Dec 11;14:1507658. doi: 10.3389/fonc.2024.1507658. eCollection 2024.
ROS1, a member of the sevenless subfamily of tyrosine kinase insulin receptors, promotes tumor cell survival, proliferation, and metastasis by activating the JAK/STAT, PI3K/AKT, and MAPK/ERK pathways. It only accounts for about 2% of total NSCLC cases. No cases of acquired ROS-1 rearrangement have been reported worldwide.
We reported a case of lung adenocarcinoma without driver alteration that developed resistance to pembrolizumab and newly emerged CD74-ROS1 fusion, and achieved a partial response after entrectinib treatment.
We hypothesize that the newly emerged ROS1 rearrangement occurs as the subset of cells harboring ROS1 gradually becomes the predominant pathological type of adenocarcinoma following pembrolizumab treatment. We propose that new therapeutic targets may emerge for this patient population following long-term immunotherapy. Thus, we advocate for regular monitoring of tumor genetic status, which could yield unexpected benefits.
ROS1是酪氨酸激酶胰岛素受体七less亚家族的成员，通过激活JAK/STAT、PI3K/AKT和MAPK/ERK途径促进肿瘤细胞的存活、增殖和转移。它仅占非小细胞肺癌（NSCLC）病例总数的约2%。全球尚未报道获得性ROS-1重排的病例。
我们报告了1例无驱动基因突变的肺腺癌病例，该病例对派姆单抗产生耐药并新出现CD74-ROS1融合，在接受恩曲替尼治疗后获得部分缓解。
我们推测，随着携带ROS1的细胞亚群在派姆单抗治疗后逐渐成为腺癌的主要病理类型，新出现的ROS1重排随之发生。我们提出，长期免疫治疗后，这一患者群体可能会出现新的治疗靶点。因此，我们主张定期监测肿瘤基因状态，这可能会带来意想不到的益处。
