Study on growth suppression of lung cancer by the inhibition of COX2,LOX, and EGFR for clinical application

本研究表明，脂氧合酶抑制剂能在体外以剂量依赖的方式抑制肺癌细胞系的增殖，部分原因是通过诱导细胞凋亡。此外，我们发现脂氧合酶抑制剂降低了各种抗癌药物的IC50值，这表明使用脂氧合酶抑制剂可能是一种很有前途的治疗方法。使用19个肺癌细胞系的小组，我们观察到吉非替尼敏感性与EGFR、HER2、HERS和HER4的表达缺乏关联。我们的结果也显示K-ras突变和对吉非替尼的敏感性之间没有明显的关联。这些数据表明，肿瘤EGFR表达与预测吉非替尼应答无临床相关性。在临床研究中，我们发现约40%的日本非小细胞肺癌患者有EGFR突变。这些突变是缺失或点突变。EGFR突变在女性、腺癌和从不吸烟者中明显频繁，EGFR突变与吉非替尼的有效性表现出良好的相关性。这些数据表明，EGFR突变可能有助于确定可能从EGFR靶向治疗中获益最多的患者群体。

This study showed that lipoxygenase inhibitors can inhibit proliferation of lung cancer cell lines in vitro in a dose-dependent manner, in part by inducing apoptosis. Moreover, we found that lipoxygenase inhibitors reduced the IC50 values of various anticancer agents, suggesting that the use of lipoxygenase inhibitors may be a promising therapeutic approach. Using a panel of 19 lung cancer cell lines, we observed the lack of association of gefitinib sensitivity with the expression of EGFR, HER2, HERS, and HER4. Our results also showed no apparent association between K-ras mutations and sensitivity to gefitinib. These data suggest that tumor EGFR expression is not clinically relevant for predicting response to gefitinib. In clinical studies, we found that about 40 % of Japanese patients with non-small cell lung cancer had EGFR mutations. The mutations were deletions or point mutations. EGFR mutations were significantly frequent in female, adenocarcinomas, and in never smokers, and EGFR mutations showed good -correlation with gefitinib effectiveness. These data suggest that EGFR mutations may help to define the patient population likely to benefit most from EGFR-targeted therapies.