University of Munich, University Hospital of Grosshadern, D-81377 Munich, Germany.
Lung Cancer. 2010 Mar;67(3):257-74. doi: 10.1016/j.lungcan.2009.10.012. Epub 2009 Nov 14.
Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer, and it is the most common cause of death in men and second only to breast cancer in women. Combination chemotherapy, usually platinum-based, is currently the first-line therapy of choice, however, the prognosis for patients with advanced NSCLC remains poor with a median survival time of 8-11 months and a 1-year survival rate of 30%. The treatment of NSCLC is therefore a major unmet need and new therapies focusing on the molecular mechanisms that mediate growth of NSCLC cells are urgently needed. The availability of agents targeted against the EGF-R, as well as the anti-VEGF agent bevacizumab, have provided some clinical benefit. Numerous other novel targeted therapies are now in clinical development and may have potential for overcoming the limitations associated with currently available drugs. In addition, a few new agents targeting novel pathways are also under clinical evaluation. The search for innovative therapeutic agents in NSCLC that are more effective and have fewer side effects than older chemotherapeutic drugs has spurred the development of more than 500 molecularly targeted agents and thereby has introduced the concept of individualized therapy. In this article we review clinical data for molecular-targeted therapies in NSCLC, with emphasis on EGF-R, VEGF-R and other novel targets. Nonetheless, for most patients with NSCLC targeted therapies have not dramatically changed clinical outcome, and resistance has emerged as a clinical problem. The molecular complexity of lung cancer underlies these disappointments and stresses the need for optimizing treatment by seeking a more personalized approach to care. Therefore, clinical trials that investigate the activity of novel agents, and incorporate patient selection based on clinical and molecular factors, are required. The increased sophistication of preclinical models and the enrollment of patients in clinical trials that include measurements of biomarkers will clearly help to identify patients who are likely to benefit from therapy, as well as further define mechanisms of resistance to therapy.
非小细胞肺癌（NSCLC）约占所有肺癌病例的 80-85%，是男性最常见的死亡原因，仅次于女性乳腺癌。联合化疗，通常基于铂类，是目前的首选一线治疗方法，然而，晚期 NSCLC 患者的预后仍然很差，中位生存时间为 8-11 个月，1 年生存率为 30%。因此，治疗 NSCLC 是一个重大的未满足需求，急需针对介导 NSCLC 细胞生长的分子机制的新疗法。针对 EGFR 的药物以及抗 VEGF 药物贝伐单抗的出现为临床提供了一些获益。目前有许多其他新型靶向疗法正在临床开发中，可能有潜力克服现有药物的局限性。此外，一些针对新途径的新型靶向药物也正在进行临床评估。为了寻找比传统化疗药物更有效、副作用更少的 NSCLC 创新治疗药物，已经开发了 500 多种针对分子靶点的药物，从而引入了个体化治疗的概念。本文综述了 NSCLC 分子靶向治疗的临床数据，重点介绍了 EGFR、VEGF-R 及其他新靶点。尽管如此，对于大多数 NSCLC 患者，靶向治疗并没有显著改变临床结局，并且已经出现了耐药性这一临床问题。肺癌的分子复杂性是导致这些失望的原因之一，强调了通过寻求更个性化的治疗方法来优化治疗的必要性。因此，需要进行临床试验以研究新型药物的活性，并根据临床和分子因素选择患者。临床前模型的日益复杂化以及包括生物标志物测量的临床试验中患者的纳入，将有助于确定可能从治疗中获益的患者，并进一步确定治疗耐药的机制。
