Development of novel molecular targeted therapies for the treatment of KRas mutated non small lung cancer using a HSP90 inhibitor

使用 HSP90 抑制剂开发治疗 KRas 突变非小细胞肺癌的新型分子靶向疗法

• 批准号: 23592078
• 负责人: MORITA ICHIRO
• 金额: $ 3.41万
• 依托单位: Kawasaki Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592078/
• 关键词: KRas; HSP90; inhibitor; AUY922; 抗腫瘍効果; 呼吸器外科学; 非小細胞性肺癌; HSP90阻害剤

Hsp90 inhibitors are substances that inhibit the activity of the Hsp90 heat shock protein. Since Hsp90 stabilizes a variety of proteins required for survival of cancer cells, these substances may have therapeutic benefit in the treatment of various types of malignancies. In the present study, we have evaluated the antitumor effects of a novel HSP90 inhibitor, AUY922 for the treatment of lung cancer. AUY922 suppressed cell viability and induced apoptosis in KRas addicted pulmonary adenocarcinoma cells. More, the inhibitor showed antitumor effect in EGFR-TK mutation or EML4-ALK positive lung cancer cells. These results indicate that AUY922 looks to be a promising treatment for non small cell lung cancer including pulmonary adenocarcinoma harboring KRas mutation.

Hsp 90抑制剂是抑制Hsp 90热休克蛋白活性的物质。由于Hsp 90稳定了癌细胞存活所需的各种蛋白质，这些物质可能在治疗各种类型的恶性肿瘤中具有治疗益处。在本研究中，我们评估了一种新的HSP 90抑制剂AUY 922治疗肺癌的抗肿瘤作用。AUY 922抑制KRas依赖性肺腺癌细胞的细胞活力并诱导细胞凋亡。此外，该抑制剂对EGFR-TK突变或EML 4-ALK阳性的肺癌细胞显示出抗肿瘤作用。这些结果表明，AUY 922看起来是一个有希望的治疗非小细胞肺癌，包括肺腺癌携带KRas突变。