Toward personalized medicine for digestive cancer patients-Development of the conventional prediction system of individual therapeutic efficacy

消化道肿瘤个体化医疗——常规个体化疗效预测系统的开发

• 批准号: 17390369
• 负责人: NISHIYAMA Masahiko
• 金额: $ 10.64万
• 依托单位: Saitama Medical University (2007)Hiroshima University (2005-2006)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390369/
• 关键词: Gene Expression Analysis; DNA microarray; Personalized Medicine; Anticancer Drugs; Gastrointestinal Cancers; Prediction of drug response; Clinical Research; Bioinformatics; 消火器がん

Enormous tasks remain to be done in the way to personalized anticancer chemotherapy. For efficacy prediction, very few critical markers have been validated to date, and a laboratory analysis system which can simultaneously predict response to several potent drugs or regimes based on understanding the interplay of multiple prediction markers has not yet been developed. In the present study (from Apr. 2005 to Mar. 2008), we newly demonstrated, developed, or identified1) potent clinical activity of weekly paclitaxel administration and docetaxel/TS-1 combination in advanced gastric cancer patients through its Phase I/II studies2) concise, accurate prediction models of the therapeutic efficacy for individual patients3) genetic polymorphisms of CYP2C8 closely related to paclitaxel-induced severe myelotoxicity in gastric cancer4)potent clinical activity of CPT-11 chemotherapy in advanced colon cancer patients through its Phase I/II studies5) concise, accurate prediction models of the therapeutic efficacy for individual patients6) genetic polymorphisms of UGT1A1 closely related to CPT-11-induced severe myelotoxicity in colon cancer, and7) novel drug sensitivity marker to CDDP, IFITM1, in esophageal cancer8)concise, accurate prediction models of the therapeutic efficacy for individual patients in esophageal cancer.These developments of a potent therapy, identification of new indicators of individual response to drugs, and concise prediction system may significantly promote a development study on personalized medicine, which would allow selection of an optimal regimen for each individual based on gene expression profile and/or genomic make-up, in gastrointestinal cancers. In parallel with the development of the prediction models for clinical responses to several active combination chemotherapies using clinical samples, a prospective clinical study to clarify the value of the prediction formulae and newly suggested indicators will commence soon.

在个性化抗癌化疗的道路上还有大量的工作要做。对于疗效预测，迄今为止已经验证的关键标志物很少，并且基于了解多种预测标志物的相互作用，可以同时预测对几种有效药物或方案的反应的实验室分析系统尚未开发。在本研究（2005年4月至2008年3月）中，我们通过I/II期研究，新证明、发展或确定了1)每周紫杉醇给药和多西紫杉醇/TS-1联合治疗晚期胃癌患者的有效临床活性。3)与紫杉醇诱导的胃癌严重髓毒性密切相关的CYP2C8基因多态性4)通过I/II期研究CPT-11化疗在晚期结肠癌患者中的有效临床活性5)简洁、准确的个体治疗疗效预测模型6)与CPT-11诱导的结肠癌严重髓毒性密切相关的UGT1A1基因多态性7)食管癌对CDDP的新型药敏标志物IFITM1。8)食管癌个体化患者疗效的简洁、准确的预测模型。这些强有力的治疗方法的发展，个体对药物反应的新指标的确定，以及简明的预测系统，可能会显著促进个体化医疗研究的发展，这将允许根据基因表达谱和/或基因组组成为胃肠道癌症的每个个体选择最佳方案。在利用临床样本开发几种有效联合化疗的临床反应预测模型的同时，一项前瞻性临床研究将很快开始，以阐明预测公式和新建议指标的价值。

项目成果

Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer

• DOI: 10.1158/1078-0432.ccr-05-2425
• 发表时间: 2006-06-01
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Yoshida, Kazuhiro;Ninomiya, Motoki;Nishiyama, Masahiko
• 通讯作者: Nishiyama, Masahiko

EGFR activating aberration occurs independently of other genetic aberrations or telomerase activation in adenocarcinoma of the lung

肺腺癌中 EGFR 激活异常的发生独立于其他遗传异常或端粒酶激活

• 发表时间: 2007
• 期刊: Oncol Rep 17
• 作者: Arifin M;Hiyama K;Tanimoto K;Wiyono WH;Hiyama E;Nishiyama M
• 通讯作者: Nishiyama M

EMP3 may be a tumor suppressor gene in late stage of neuroblastoma development

EMP3可能是神经母细胞瘤发展晚期的抑癌基因

• 发表时间: 2008
• 作者: Fukuba I;Hiyama K;Kamimatsuse A;Yamaoka H;Fukuda E;Tazaki T;Hiyama E
• 通讯作者: Hiyama E

Possible mechanism of lung adenocarcinoma development from telomerase-positive "stem cells" free from cellular senescence.

肺腺癌从端粒酶阳性“干细胞”发展而来的可能机制，不受细胞衰老的影响。

• 发表时间: 2008
• 作者: Fukuba I;Hiyama K;Kamimatsuse A;Tazaki T;Yamaoka H;Fukuda E;Arifin M;Fumoto S;Tanimoto K;Nishiyama M;Hiyama E;Arifin M.
• 通讯作者: Arifin M.

Relationship between p16 inactivation and telomerase activation mechanism in lung adenocarcinoma.

肺腺癌中p16失活与端粒酶激活机制的关系。

• 发表时间: 2007
• 作者: Arifin M;Hiyama K;Tanimoto K;Hiyama E;Nishiyama M;Arifin M.;麓 祥一;中村秀明;Arifin M.
• 通讯作者: Arifin M.