Fong Kwun M, Minna John D
Prince Charles Hospital, Chermside, Brisbane, Australia.
Clin Chest Med. 2002 Mar;23(1):83-101. doi: 10.1016/s0272-5231(03)00062-5.
This review summarizes the rapidly expanding knowledge of the molecular pathogenesis of lung cancer. It is clear that respiratory epithelial cells require many genetic alterations to become invasive and metastatic cancer. Much more is to be learned, but with modern technology. Clinicians can detect "field cancerized" regions and preneoplastic and malignant cells, therefore offering the opportunity to intercede with biomarker-monitored prevention and early detection efforts. Such molecular screening and detection efforts will likely be coupled to advances in low-dose computed tomographic imaging, positron emission tomography scans, and other imaging modalities. Although this molecular marker approach has great potential, there is not yet a molecular marker validated in large prospective trials that has major independent predictive prognostic value. There is an urgent need for large, adequately powered, carefully designed prospective studies to identify clinically useful new biomarkers. Finally, new therapeutic strategies with genetic manipulation, small molecules, antibodies, vaccines, and, particularly, new drugs targeting specific biologic pathways found to be abnormal in lung provide for future optimism. Researchers need to define their individual value, especially when integrated with standard therapies.
本综述总结了肺癌分子发病机制方面迅速增长的知识。显然，呼吸道上皮细胞需要许多基因改变才能成为侵袭性和转移性癌症。尽管还有很多有待了解，但借助现代技术，临床医生能够检测出“场癌化”区域以及癌前和恶性细胞，从而为通过生物标志物监测的预防和早期检测工作提供了干预机会。这种分子筛查和检测工作可能会与低剂量计算机断层扫描成像、正电子发射断层扫描及其他成像方式的进展相结合。尽管这种分子标记方法具有巨大潜力，但在大型前瞻性试验中尚未有经过验证的具有重大独立预测预后价值的分子标记物。迫切需要开展大规模、有足够效力、精心设计的前瞻性研究，以确定临床上有用的新生物标志物。最后，基因操作、小分子、抗体、疫苗等新的治疗策略，尤其是针对肺癌中发现的特定异常生物途径的新药，为未来带来了希望。研究人员需要确定它们各自的价值，特别是在与标准疗法联合使用时。
