De Novo Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in EGFR Mutation-Positive Patients with Non-small Cell Lung Cancer
De Novo Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in EGFR Mutation-Positive Patients with Non-small Cell Lung Cancer
复制标题
DOI：
10.1097/jto.0b013e3181cee47e
复制
发表时间：
2010-03-01
影响因子：
20.4
通讯作者：
Nakagawa, Kazuhiko
中科院分区：
文献类型：
--
作者：
Takeda, Masayuki;Okamoto, Isamu;Nakagawa, Kazuhiko
背景：表皮生长因子受体 (EGFR) 基因的体细胞突变是非小细胞肺癌 (NSCLC) 患者对 EGFR 酪氨酸激酶抑制剂 (TKI) 治疗反应的预测因子。然而，携带 EGFR 突变的患者对这些药物的从头耐药机制仍不清楚。我们检查了 KRAS 的突变状态是否可能与 EGFR 突变阳性 NSCLC 患者对 EGFR-TKI 的原发耐药相关。 方法：40 名接受吉非替尼或厄洛替尼治疗且有存档组织标本的 EGFR 突变 NSCLC 患者纳入本研究。通过直接测序分析 KRAS 突变。结果：40 名患者中的 3 名 (7.5%) 患有进展性疾病，这 3 名患者中的 2 名 (67%) 同时具有 KRAS 和 EGFR 突变。结论：我们的结果表明，KRAS 突变是 EGFR 突变阳性 NSCLC 患者对 EGFR-TKI 反应的阴性预测因子。
Background: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are a predictor of response to treatment with EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, mechanisms of de novo resistance to these drugs in patients harboring EGFR mutations have remained unclear. We examined whether the mutational status of KRAS might be associated with primary resistance to EGFR-TKIs in EGFR mutation-positive patients with NSCLC.Methods: Forty patients with NSCLC with EGFR mutations who were treated with gefitinib or erlotinib and had archival tissue specimens available were enrolled in the study. KRAS mutations were analyzed by direct sequencing.Results: Three (7.5%) of the 40 patients had progressive disease, and two (67%) of these three individuals had both KRAS and EGFR mutations.Conclusions: Our results suggest that KRAS mutation is a negative predictor of response to EGFR-TKIs in EGFR mutation-positive patients with NSCLC.