Ma Li, Zhang Shucai
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Zhongguo Fei Ai Za Zhi. 2013 Dec;16(12):671-5. doi: 10.3779/j.issn.1009-3419.2013.12.10.
Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.
肺鳞状细胞癌(SQCLC)是全球最常见的肺癌亚型之一,全球约有40万人死于肺鳞状细胞癌,其发病机制与烟草暴露密切相关。不幸的是,肺鳞状细胞癌患者并未从靶向治疗的重大进展中获益,比如表皮生长因子受体(EGFR)抑制剂或间变性淋巴瘤激酶(ALK)抑制剂,这些药物分别在具有EGFR突变的肺腺癌或棘皮动物微管相关蛋白样4(EML4)-ALK融合的肺腺癌中显示出卓越的活性。目前已投入大量精力来描绘肺鳞状细胞癌的基因组特征。这些努力产生的新成果包括成纤维细胞生长因子受体1(FGFR1)基因的扩增、盘状结构域受体2(DDR2)基因突变,它们是治疗肺鳞状细胞癌的潜在新靶点。研究人员发现,肺鳞状细胞癌患者的基因组中有许多特定的分子靶向基因。这些变化在细胞周期调控、氧化应激、细胞凋亡、鳞状上皮分化中起着至关重要的作用,可能是肺鳞状细胞癌的候选靶向分子。在此,我们对这些发现及其对评估针对这些靶点的新型疗法价值的肺鳞状细胞癌临床试验的意义进行综述。