Johnson Jackie L, Pillai Smitha, Chellappan Srikumar P
Cancer Biology Ph.D. Program, University of South Florida, Tampa, FL 33612, USA.
Biochem Res Int. 2012;2012:940405. doi: 10.1155/2012/940405. Epub 2012 Aug 15.
Despite significant advances in the detection and treatment of lung cancer, it causes the highest number of cancer-related mortality. Recent advances in the detection of genetic alterations in patient samples along with physiologically relevant animal models has yielded a new understanding of the molecular etiology of lung cancer. This has facilitated the development of potent and specific targeted therapies, based on the genetic and biochemical alterations present in the tumor, especially non-small-cell lung cancer (NSCLC). It is now clear that heterogeneous cell signaling pathways are disrupted to promote NSCLC, including mutations in critical growth regulatory proteins (K-Ras, EGFR, B-RAF, MEK-1, HER2, MET, EML-4-ALK, KIF5B-RET, and NKX2.1) and inactivation of growth inhibitory pathways (TP53, PTEN, p16, and LKB-1). How these pathways differ between smokers and non-smokers is also important for clinical treatment strategies and development of targeted therapies. This paper describes these molecular targets in NSCLC, and describes the biological significance of each mutation and their potential to act as a therapeutic target.
尽管在肺癌的检测和治疗方面取得了重大进展，但它仍是导致癌症相关死亡人数最多的疾病。患者样本中基因改变检测技术的最新进展以及生理相关动物模型的建立，使人们对肺癌的分子病因有了新的认识。这促进了基于肿瘤中存在的基因和生化改变，尤其是非小细胞肺癌（NSCLC）的强效和特异性靶向治疗的发展。现在很清楚，异质性细胞信号通路被破坏会促进NSCLC的发生，包括关键生长调节蛋白（K-Ras、EGFR、B-RAF、MEK-1、HER2、MET、EML-4-ALK、KIF5B-RET和NKX2.1）的突变以及生长抑制通路（TP53、PTEN、p16和LKB-1）的失活。这些通路在吸烟者和非吸烟者之间的差异对于临床治疗策略和靶向治疗的开发也很重要。本文描述了NSCLC中的这些分子靶点，并阐述了每个突变的生物学意义及其作为治疗靶点的潜力。
