Alberta: Tom Baker Cancer Centre and University of Calgary, Calgary (Bebb); Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton (Bigras); Cross Cancer Institute and University of Alberta, Edmonton (Butts); Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, and Calgary Laboratory Services, Calgary (Rashid-Kolvear).
Quebec: Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal (Agulnik); Department of Pathology, Centre hospitalier de l'Université de Montréal, Montreal (Albadine); Service d'anatomopathologie et de cytologie, Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, Quebec City (Couture, Desmeules).
Curr Oncol. 2019 Aug;26(4):e551-e557. doi: 10.3747/co.26.5137. Epub 2019 Aug 1.
The ros1 kinase is an oncogenic driver in non-small-cell lung cancer (nsclc). Fusion events involving the gene are found in 1%-2% of nsclc patients and lead to deregulation of a tyrosine kinase-mediated multi-use intracellular signalling pathway, which then promotes the growth, proliferation, and progression of tumour cells. fusion is a distinct molecular subtype of nsclc, found independently of other recognized driver mutations, and it is predominantly identified in younger patients (<50 years of age), women, never-smokers, and patients with adenocarcinoma histology. Targeted inhibition of the aberrant ros1 kinase with crizotinib is associated with increased progression-free survival (pfs) and improved quality-of-life measures. As the sole approved treatment for rearranged nsclc, crizotinib has been demonstrated, through a variety of clinical trials and retrospective analyses, to be a safe, effective, well-tolerated, and appropriate treatment for patients having the rearrangement. Canadian physicians endorse current guidelines which recommend that all patients with nonsquamous advanced nsclc, regardless of clinical characteristics, be tested for rearrangement. Future integration of multigene testing panels into the standard of care could allow for efficient and cost-effective comprehensive testing of all patients with advanced nsclc. If a rearrangement is found, treatment with crizotinib, preferably in the first-line setting, constitutes the standard of care, with other treatment options being investigated, as appropriate, should resistance to crizotinib develop.
ROS1 激酶是一种非小细胞肺癌（NSCLC）的致癌驱动基因。在 1%-2%的 NSCLC 患者中发现涉及基因的融合事件，导致酪氨酸激酶介导的多用途细胞内信号通路失调，从而促进肿瘤细胞的生长、增殖和进展。ROS1 融合是 NSCLC 的一个独特的分子亚型，独立于其他公认的驱动突变而存在，主要发生在年轻患者（<50 岁）、女性、从不吸烟者和腺癌组织学患者中。针对异常 ROS1 激酶的靶向抑制作用，使用克唑替尼，与无进展生存期（PFS）的延长和生活质量的改善相关。作为唯一批准用于治疗重排型 NSCLC 的药物，克唑替尼通过多种临床试验和回顾性分析证明，对于存在 ROS1 重排的患者是一种安全、有效、耐受良好且合适的治疗方法。加拿大医生支持当前的指南，建议对所有非鳞状晚期 NSCLC 患者，无论临床特征如何，都进行 ROS1 重排检测。未来，将多基因检测面板纳入标准治疗可能会允许对所有晚期 NSCLC 患者进行高效且具有成本效益的综合检测。如果发现存在 ROS1 重排，使用克唑替尼进行治疗（最好是一线治疗）是标准治疗方法，应根据需要调查其他治疗选择，以应对对克唑替尼的耐药性。
