表皮生长因子受体通路阻断治疗晚期非小细胞肺癌

Update on targeting EGFR in advanced non-small-cell lung cancer

化学治疗晚期非小细胞肺癌(NSCLC)疗效已达到平台,靶向药物是进一步提高疗效的关键.表皮生长因子受体(EGFR)信号异常在NSCLC的发生和进展中起重要作用,已成为抗肿瘤治疗的常用靶点.研究显示,小分子口服EGFR酪氨酸激酶抑制剂吉非替尼和厄洛替尼毒副作用轻微,对化疗失败的NSCLC患者可以改善症状、提高生活质量、延长生存.此外,抗EGFR单克隆抗体西妥昔单抗(cetuximab)在晚期NSCLC的一线和二线治疗中均显示出令人鼓舞的疗效.第二代靶向治疗药物--多靶点抑制剂,可同时阻断肿瘤多个信号传导,临床试验初步结果表明,毒副作用可以耐受,治疗晚期NSCLC有较好的应用前景.

The results of chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC)had reached a plateau.Targeted therapy is the key to improving efficacy.In the last 5 years the epidermal growth factor receptor(EGFR)has emerged as one of the most important targets for drug development in oncology.Small molecules that inhibit the tyrosine kinase(TK)domain of EGFR have become new critical weapons in the treatment of NSCLC.Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefit when combined with chemotherapy.Recent data suggest that multitargeted inhibitors might have greater activity owing to their ability to simultaneously block key signaling pathways.Preliminary results of such agents in clinical trials shows that they have a well-tolerated toxicity profile,and might have a promising value in the treatment of advanced non-small-cell lung cancer.