Toloza Eric M, Morse Michael A, Lyerly H Kim
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Cell Biochem. 2006 Sep 1;99(1):1-22. doi: 10.1002/jcb.20851.
Lung cancer patients suffer a 15% overall survival despite advances in chemotherapy, radiation therapy, and surgery. This unacceptably low survival rate is due to the usual finding of advanced disease at diagnosis. However, multimodality strategies using conventional therapies only minimally improve survival rates even in early stages of lung cancer. Attempts to improve survival in advanced disease using various combinations of platinum-based chemotherapy have demonstrated that no regimen is superior, suggesting a therapeutic plateau and the need for novel, more specific, and less toxic therapeutic strategies. Over the past three decades, the genetic etiology of cancer has been gradually delineated, albeit not yet completely. Understanding the molecular events that occur during the multistep process of bronchogenic carcinogenesis may make these tasks more surmountable. During these same three decades, techniques have been developed which allow transfer of functional genes into mammalian cells. For example, blockade of activated tumor-promoting oncogenes or replacement of inactivated tumor-suppressing or apoptosis-promoting genes can be achieved by gene therapy. This article will discuss the therapeutic implications of these molecular changes associated with bronchogenic carcinomas and will then review the status of gene therapies for treatment of lung cancer.
尽管化疗、放疗和手术取得了进展，但肺癌患者的总体生存率仍为15%。这种低得令人无法接受的生存率是由于在诊断时通常发现疾病已处于晚期。然而，即使在肺癌早期，仅使用传统疗法的多模式策略对生存率的提高也微乎其微。尝试使用各种铂类化疗组合来提高晚期疾病的生存率已表明，没有一种方案具有优越性，这表明存在治疗平台期，需要新的、更具特异性且毒性更小的治疗策略。在过去三十年中，癌症的遗传病因已逐渐被阐明，尽管尚未完全阐明。了解在支气管源性癌发生的多步骤过程中发生的分子事件可能会使这些任务更易于克服。在这相同的三十年中，已开发出允许将功能基因转移到哺乳动物细胞中的技术。例如，通过基因疗法可以实现对激活的促肿瘤癌基因的阻断或对失活的肿瘤抑制基因或促凋亡基因的替代。本文将讨论与支气管源性癌相关的这些分子变化的治疗意义，然后回顾肺癌基因治疗的现状。
