Medical Oncology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
Cancer Treat Rev. 2012 Feb;38(1):36-53. doi: 10.1016/j.ctrv.2011.04.001. Epub 2011 May 17.
Lung cancer remains the leading cause of malignancy-related mortality worldwide, with over one million cases diagnosed yearly. Non-small-cell lung cancer (NSCLC) accounts for >80% of all lung cancers. Because lung cancer is typically diagnosed at an advanced stage, chemotherapy (CT) is the mainstay of management. Conventional treatment of NSCLC has apparently reached a plateau of effectiveness in improving survival of patients, and treatment outcomes must still be considered disappointing. Hence, considerable efforts have been made in order to identify novel targeted agents that interfere with other dysregulated pathways in advanced NSCLC patients. In order to further improve the results of targeted therapy, we should not forget that lung cancer is a heterogeneous disease with multiple mutations, and it is unlikely that any single signaling pathway drives the oncogenic behaviour of all tumours. The relative failure of some targeted therapies may be a result of multilevel cross-stimulation among the targets of the new biological agents along several pathways of signal transduction that lead to neoplastic events. Thus, blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. We summarize the most promising research approaches to the treatment of NSCLC, with particular attention to drugs with multiple targets or combining targeted therapies.
肺癌仍然是全球恶性肿瘤相关死亡率的主要原因，每年诊断出超过 100 万例。非小细胞肺癌 (NSCLC) 占所有肺癌的>80%。由于肺癌通常在晚期诊断，化疗 (CT) 是治疗的主要手段。传统的 NSCLC 治疗显然已经达到了提高患者生存的效果的瓶颈，并且治疗结果仍被认为令人失望。因此，人们已经做出了相当大的努力来寻找新的靶向药物，这些药物可以干扰晚期 NSCLC 患者中其他失调的途径。为了进一步提高靶向治疗的效果，我们不应忘记，肺癌是一种具有多种突变的异质性疾病，不太可能有任何单一的信号通路驱动所有肿瘤的致癌行为。一些靶向治疗的相对失败可能是由于新的生物制剂的靶点之间的多层次交叉刺激，这些靶点沿着导致肿瘤发生的信号转导途径的几个途径进行。因此，仅阻断这些途径中的一个允许其他途径作为癌细胞的挽救或逃逸机制。我们总结了治疗 NSCLC 的最有前途的研究方法，特别关注具有多个靶点或联合靶向治疗的药物。
