精准医疗在非小细胞肺癌中的应用  

Application of precision medicine in non-small cell lung cancer

作　　者：刘鹏飞[1] 张会来[1] 

机构地区：[1]天津医科大学肿瘤医院淋巴瘤内科,中美淋巴血液肿瘤诊治中心,天津市“肿瘤防治”重点实验室,国家肿瘤临床医学研究中心,300060

出　　处：《国际生物医学工程杂志》2015年第4期247-252,共6页International Journal of Biomedical Engineering

摘　　要：肺癌是全球发病率和死亡率增长最快，对人类健康和生命威胁最大的恶性肿瘤之一。下一代基因测序技术的应用为非小细胞肺癌（NSCLC）不同亚型的全面分析提供了平台。在NSCLC／患者基因组中，已鉴定出一些高频突变的基因，如克尔斯滕大鼠肉瘤病毒癌同源（KRAS）基因、肿瘤蛋白53（TP53）基因和表皮生长因子受体（EGFR）基因。虽然使用靶向EGFR和间变性淋巴瘤激酶基因（ALK）的精准治疗非常成功，但大部分NSCLC患者的这2个基因并不发生改变。汇集了目前针对肺腺癌（LAC）和鳞状细胞癌（SCC）的模式疗法并分析了其所对应的异常基因，及主要针对由KRAS、TP53等目前尚无靶向药物的突变靶点导致肿瘤的新型治疗策略。研究表明，只有在分子层面上深度解读NSCLC的致癌基因，运用高通量测序技术，才能实现NSCLC的精准治疗，大幅度降低肺癌的高死亡率。Lung cancer, with growing morbidity and mortality worldwide, is one of the most malignant tumors, representing a significant threat to human health and fife. The application of next-generation genomic technologies has offered a more comprehensive look at the mutational landscape across the different subtypes of non- small cell lung cancer （NSCLC）. A number of recurrent mutations such as TP53, KRAS, and epidermal growth factor receptor （EGFR） have been identified in NSCLC. While targeted therapeutic successes have been demonstrated in the therapeutic targeting of EGFR and ALK, the majority of NSCLC tumors do not harbor these genomie events. This review looks at the current treatment paradigms for lung adenocarcinomas （LAC） and squamous cell carcinomas, examining genomic aberrations that dictate therapy selection, as well as novel therapeutic strategies for tumors harboring mutations in KRAS and TP53 which, to date, have been considered ＂undrnggable＂. A more thorough understanding of the molecular alterations that govern NSCLC tumorigenesis, aided by next-generation sequencing, will lead to targeted therapeutic options expected to dramatically reduce the high mortality observed in lung cancer.

关 键 词：非小细胞肺癌 精准医疗 表皮生长因子受体 克尔斯滕大鼠肉瘤病毒癌同源 肿瘤蛋白53 

分 类 号：R734.2[医药卫生—肿瘤] Q78[医药卫生—临床医学]