Human Pathology Department, Medical Oncology Unit, University of Messina, Italy.
Expert Rev Respir Med. 2011 Jun;5(3):413-24. doi: 10.1586/ers.11.27.
In recent years, the management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib in patients with mutations in the epidermal growth factor receptor (EGFR). Erlotinib was introduced as a second- and third-line therapy for advanced non-small-cell lung cancer and demonstrated a survival advantage over placebo in unselected patients. Gefitinb did not confer the same advantage but specific subgroups of patients obtained higher response rates. The discovery of EGFR mutations explained the molecular mechanism of sensitivity to TKIs, and several clinical trials have evaluated the efficacy of TKIs in EGFR-mutated patients. New molecular alterations involving different genes have also been described and associated with sensitivity or resistance to TKIs. The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to erlotinib and gefitinib.
近年来，肺癌的治疗已朝着分子指导治疗的方向发展，这种新方法的最佳例子是使用表皮生长因子受体 (EGFR) 突变的酪氨酸激酶抑制剂 (TKI) 厄洛替尼和吉非替尼。厄洛替尼被引入作为晚期非小细胞肺癌的二线和三线治疗药物，在未选择的患者中比安慰剂具有生存优势。吉非替尼没有带来相同的优势，但特定的患者亚组获得了更高的反应率。EGFR 突变的发现解释了对 TKI 敏感的分子机制，并且已经进行了几项临床试验来评估 TKI 在 EGFR 突变患者中的疗效。还描述了涉及不同基因的新的分子改变，并与 TKI 的敏感性或耐药性相关。对反应的分子预测因子的鉴定可以允许选择最有可能对厄洛替尼和吉非替尼有反应的患者。
