Department of Medical Oncology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
J Thorac Oncol. 2010 Mar;5(3):399-400. doi: 10.1097/JTO.0b013e3181cee47e.
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.
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.
Three (7.5%) of the 40 patients had progressive disease, and two (67%) of these three individuals had both KRAS and EGFR mutations.
Our results suggest that KRAS mutation is a negative predictor of response to EGFR-TKIs in EGFR mutation-positive patients with NSCLC.
表皮生长因子受体 (EGFR) 基因的体细胞突变是预测非小细胞肺癌 (NSCLC) 患者对 EGFR 酪氨酸激酶抑制剂 (TKI) 治疗反应的指标。然而，携带 EGFR 突变的患者对这些药物产生新的耐药性的机制仍不清楚。我们研究了 KRAS 突变状态是否与 EGFR 突变阳性 NSCLC 患者对 EGFR-TKI 的原发性耐药有关。
本研究纳入了 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 突变阳性 NSCLC 患者。通过直接测序分析 KRAS 突变。
40 名患者中有 3 名（7.5%）出现疾病进展，其中 2 名（67%）患者同时存在 KRAS 和 EGFR 突变。
我们的结果表明，KRAS 突变是 EGFR 突变阳性 NSCLC 患者对 EGFR-TKI 反应的负预测因子。
