Division of Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ontario, Canada.
J Thorac Oncol. 2012 Mar;7(3):609-20. doi: 10.1097/JTO.0b013e3182435f3e.
We aim to describe the molecular mechanisms relevant to angiogenesis inhibition and to critically evaluate the current evidence for the use of angiogenic inhibitors (AIs) in the treatment of non-small cell lung cancer (NSCLC).
The literature on the basic concepts of tumor angiogenesis is reviewed. Published articles and major lung cancer conference abstracts were screened for reports on the use of AI in NSCLC patients and the National Institutes of Health clinical trials database was searched for relevant ongoing studies.
We delineate in this review the molecular and cellular aspects of angiogenesis and vasculogenesis and outline the relevance of these to lung cancer. Clinical studies of AIs in NSCLC reported to date as well ongoing studies are summarized. Major issues discussed include the choice of the right molecular target; characteristics of various tyrosine kinase inhibitors; potential drawbacks and concerns regarding the application of AIs in clinical practice, and major unanswered questions and future directions.
AIs have antitumor activity in NSCLC and have become part of the standard of care for patients with advanced nonsquamous cell carcinoma. Unfortunately, the gains have been modest and robust predictive biomarkers are urgently needed. Clinical trials to date have validated the tumor vasculature as a legitimate target, and as our understanding of the biology of tumor angiogenesis increases, exciting new therapeutic approaches are being explored.
我们旨在描述与血管生成抑制相关的分子机制,并批判性地评估当前在非小细胞肺癌(NSCLC)治疗中使用血管生成抑制剂(AIs)的证据。
综述了肿瘤血管生成的基本概念文献。筛选了关于 AI 在 NSCLC 患者中应用的已发表文章和主要肺癌会议摘要,并在国立卫生研究院临床试验数据库中搜索了相关的正在进行的研究。
我们在这篇综述中描述了血管生成和血管发生的分子和细胞方面,并概述了这些方面与肺癌的相关性。总结了迄今为止报道的 NSCLC 中 AIs 的临床研究以及正在进行的研究。讨论的主要问题包括选择正确的分子靶点;各种酪氨酸激酶抑制剂的特征;在临床实践中应用 AIs 的潜在缺点和关注点,以及主要的未解决问题和未来方向。
AIs 在 NSCLC 中有抗肿瘤活性,已成为晚期非鳞状细胞癌患者标准治疗的一部分。不幸的是,这些收益是适度的,迫切需要强有力的预测生物标志物。迄今为止的临床试验已经验证了肿瘤血管系统是一个合理的靶点,随着我们对肿瘤血管生成生物学的理解的增加,令人兴奋的新治疗方法正在探索中。