Medical Oncology Department, Civil Hospital of Livorno, Istituto Toscano Tumori , Viale Alfieri 36, 57100, Livorno , Italy +39 0586 223189 ; +39 0586 223457 ;
Expert Opin Biol Ther. 2013 Oct;13(10):1401-12. doi: 10.1517/14712598.2013.827657. Epub 2013 Aug 10.
Activating mutations of the epidermal growth factor receptor (EGFR) gene and rearrangement of anaplastic lymphoma kinase (ALK) gene best illustrate the therapeutic relevance of molecular characterization in non-small cell lung cancer (NSCLC) patients. Several genetic aberrations with a potential prognostic or predictive role have been identified, mainly in adenocarcinoma subtype, including ROS1, RET, MET, HER2, BRAF and KRAS. More recently oncogenic drivers, such as DDR2, FGFR1 and PI3KCA, have been characterized in squamous cell lung carcinoma (SCC) and target agents are currently under evaluation. The aim of this review is to summarize the growing scenario of new targetable oncogenes in NSCLC.
For this review article all published data on NSCLC genomic alterations, including the techniques employed for oncogenic drivers identification, the prevalence of each one in lung cancer subtypes, the preclinical data corroborating their role in tumorigenesis and the potential biological tailored agents tested and under evaluation were collected and analyzed using PubMed.
Oncogenic products represent reliable targets for drug therapy and the expanding knowledge of molecular pathways involved in lung tumorigenesis is resulting in a dramatic change of treatment strategies leading to an improvement in disease and symptom control, extending life duration and improving quality of life.
表皮生长因子受体 (EGFR) 基因的激活突变和间变性淋巴瘤激酶 (ALK) 基因的重排最能说明非小细胞肺癌 (NSCLC) 患者分子特征的治疗相关性。已经确定了几种具有潜在预后或预测作用的遗传异常,主要在腺癌亚型中,包括 ROS1、RET、MET、HER2、BRAF 和 KRAS。最近,在鳞状细胞肺癌 (SCC) 中也对 DDR2、FGFR1 和 PI3KCA 等致癌驱动基因进行了特征描述,目前正在评估靶向药物。本文旨在总结 NSCLC 中不断增多的可靶向致癌基因。
为了撰写这篇综述文章,我们收集并分析了所有关于 NSCLC 基因组改变的已发表数据,包括用于鉴定致癌驱动基因的技术、每种驱动基因在肺癌亚型中的发生率、支持其在肿瘤发生中作用的临床前数据,以及已测试和正在评估的潜在生物靶向药物。
致癌产物是药物治疗的可靠靶点,对参与肺肿瘤发生的分子途径的不断扩展的认识正在导致治疗策略的巨大变化,从而改善疾病和症状控制,延长生存时间并提高生活质量。