Salgia R, Skarin A T
Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Clin Oncol. 1998 Mar;16(3):1207-17. doi: 10.1200/JCO.1998.16.3.1207.
To review several recently described molecular abnormalities in lung cancer and discuss their potential diagnostic and therapeutic relevance.
Articles were identified through a Medline search (1966 to 1997) and studies, including reviews, were cited in the references.
Molecular mechanisms altered in lung cancer include induced expression of oncogenes, such as RAS, MYC, c-erbB-2, and BCL-2, and loss of tumor-suppressor genes, such as RB, p53, and p16INK4A. RAS is a 21-kd G protein and up to 30% of adenocarcinomas show mutations in K-RAS oncogene. MYC encodes a transcriptional activator and amplification may adversely affect survival in small-cell lung cancer (SCLC). The growth factor receptor c-erbB-2 is overexpressed in up to 25% of non-small-cell lung cancer (NSCLC) cases. BCL-2, a negative regulator of apoptosis, is expressed differently in some NSCLCs. Abnormalities of RB, a key regulator of cell cycle, are detected in greater than 90% of SCLCs. There is an inverse relationship in lung cancer cells between expression of RB and p16INK4A, an upstream regulator of RB. Mutations of p53, with frequencies up to 50% in NSCLC and 80% in SCLC, can lead to loss of tumor-suppressor function, cellular proliferation, and inhibition of apoptosis. The identified molecular abnormalities in lung cancer are currently used to develop diagnostics for detecting early disease, as well as to identify targets for gene therapy.
Genetic abnormalities involved in the pathogenesis of lung cancer are rapidly being delineated. Understanding molecular abnormalities in lung cancer could potentially lead to earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.
回顾近期描述的肺癌中几种分子异常情况，并讨论其潜在的诊断和治疗意义。
通过Medline检索（1966年至1997年）确定文章，并在参考文献中引用了包括综述在内的研究。
肺癌中改变的分子机制包括癌基因如RAS、MYC、c-erbB-2和BCL-2的诱导表达，以及肿瘤抑制基因如RB、p53和p16INK4A的缺失。RAS是一种21-kd的G蛋白，高达30%的腺癌显示K-RAS癌基因发生突变。MYC编码一种转录激活因子，其扩增可能对小细胞肺癌（SCLC）的生存产生不利影响。生长因子受体c-erbB-2在高达25%的非小细胞肺癌（NSCLC）病例中过度表达。BCL-2是细胞凋亡的负调节因子，在一些NSCLC中表达不同。RB是细胞周期的关键调节因子，在超过90%的SCLC中检测到异常。肺癌细胞中RB和p16INK4A（RB的上游调节因子）的表达呈负相关。p53突变在NSCLC中的频率高达50%，在SCLC中高达80%，可导致肿瘤抑制功能丧失、细胞增殖和细胞凋亡抑制。目前已利用肺癌中确定的分子异常来开发早期疾病检测诊断方法，并确定基因治疗靶点。
肺癌发病机制中涉及的基因异常正在迅速被阐明。了解肺癌中的分子异常可能会导致早期诊断，并开发新的肺癌治疗研究方法。
