A study on the mechanisms underlying resistance acquisition of lung cancer for tyrosine kinase inhibitors

肺癌酪氨酸激酶抑制剂获得耐药机制的研究

• 批准号: 21590384
• 负责人: JIANG Shi-xu
• 金额: $ 2.91万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590384/
• 关键词: 肺癌; EGFR; Met; 分子標的抗腫瘍薬; 薬剤耐性; MET

Tyrosine kinase inhibitor(TKI) is effective for lung cancers with EGFR mutation, but these tumors eventually acquire drug resistance. In the present study, we found that some TKI-treated tumors mainly composed of EGFR-wild tumor dells while the EGFR-mutant ones vanished or markedly decreased, and their pre-treated tumors contained EGFR-wild tumor cells. Furthermore, with surgically resected TKI-untreated cases, we showed that most EGFR-mutant tumors also contained EGFR-wild tumor cells. Thus, multiple mechanisms underline acquired TKI resistance, and besides the reported secondary EGFR T790M mutation and adaptive Met amplification, the selective survival of the preexisting TKI-resistant EGFR-wild tumor cells also contributes to the drug acquisition.

酪氨酸激酶抑制剂（TKI）对EGFR突变的肺癌有效，但这些肿瘤最终获得耐药性。在本研究中，我们发现一些TKI治疗的肿瘤主要由EGFR野生型肿瘤细胞组成，而EGFR突变型肿瘤细胞消失或明显减少，并且其预治疗的肿瘤含有EGFR野生型肿瘤细胞。此外，对于手术切除的TKI未治疗的病例，我们发现大多数EGFR突变型肿瘤也含有EGFR野生型肿瘤细胞。因此，多种机制强调了获得性TKI耐药，除了报告的继发性EGFR T790 M突变和适应性Met扩增外，预先存在的TKI耐药EGFR野生型肿瘤细胞的选择性存活也有助于药物获得。

项目成果

Prognostic Significance of Nestin Expression in Resected Non-small Cell Lung Cancer

• DOI: 10.1378/chest.10-1121
• 发表时间: 2011-04-01
• 期刊: CHEST
• 影响因子: 9.6
• 作者: Ryuge, Shinichiro;Sato, Yuichi;Masuda, Noriyuki
• 通讯作者: Masuda, Noriyuki

Anti-HuC and-HuD autoantibodies are differential ero-diagnostic markers for small cell carcinoma from large cell neuroendocrine carcinoma of the lung

抗 HuC 和 HuD 自身抗体是小细胞癌与大细胞肺癌神经内分泌癌的鉴别诊断标志物

• 发表时间: 2012
• 期刊: Int J Oncol
• 影响因子: 5.2
• 作者: Matsumoto T;Rygue S Kobayashi M;Kageyama T;Hattori M;Goshima N;Jiang SX;Saegusa M;Iyoda A;Satoh Y;Masuda N;Sato Y
• 通讯作者: Sato Y

Expression of RACK1 is a novel biomarker in pulmonary adenocarcinomas

• DOI: 10.1016/j.lungcan.2009.09.015
• 发表时间: 2010-07-01
• 期刊: LUNG CANCER
• 影响因子: 5.3
• 作者: Nagashio, Ryo;Sato, Yuichi;Okayasu, Isao
• 通讯作者: Okayasu, Isao

Thymic large cell neuroendocrine carcinoma: report of a resected case - a case report

• DOI: 10.1186/1749-8090-5-115
• 发表时间: 2010-11-22
• 期刊: JOURNAL OF CARDIOTHORACIC SURGERY
• 影响因子: 1.6
• 作者: Ogawa, Fumihiro;Iyoda, Akira;Satoh, Yukitoshi
• 通讯作者: Satoh, Yukitoshi

HADHA is a potential predictor of response to platinum-based chemotherapy for lung cancer.

• 发表时间: 2011
• 期刊: Asian Pacific journal of cancer prevention : APJCP
• 作者: Taihei Kageyama;R. Nagashio;S. Ryuge;Toshihide Matsumoto;A. Iyoda;Y. Satoh;N. Masuda;Shi‐Xu Jiang;M. Saegusa;Yuichi Sato