Individualized Cancer Therapy Using Cancer Testis Antigens

使用癌症睾丸抗原的个体化癌症治疗

• 批准号: 22650233
• 负责人: MIYAGAWA Kiyoshi
• 金额: $ 2.17万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22650233/
• 关键词: がん精巣抗原; 相同組換え修復; 放射線治療; 化学療法; 個別化治療; 感受性予測

Cancer testis antigens are assumed to be excellent targets for cancer treatment because their expression is limited to germ cells and cancers of various origins. We investigated therapeutic strategies for cancer expressing these molecules by analyzing their functions. We confirmed that SYCP3 and SMC1., components of synaptonemal complexes formed during meiosis, are cancer testis antigens, and found that their expression in somatic cells inhibits homologous recombination repair of DNA double-stranded breaks. This result indicates that cancers expressing these cancer testis antigens are hypersensitive to treatments that exert anti-tumor activities by inducing DNA double-stranded breaks.

癌症睾丸抗原被认为是癌症治疗的极好靶点，因为它们的表达限于生殖细胞和各种起源的癌症。我们通过分析这些分子的功能来研究表达这些分子的癌症的治疗策略。我们证实SYCP3和SMC1.，减数分裂期间形成的联会复合体的组分是癌症睾丸抗原，并且发现它们在体细胞中的表达抑制DNA双链断裂的同源重组修复。该结果表明，表达这些癌睾丸抗原的癌症对通过诱导DNA双链断裂而发挥抗肿瘤活性的治疗过敏。

项目成果

Ataxia Telangiectasia Mutated (ATM)-mediated DNA Damage Response in Oxidative Stress-induced Vascular Endothelial Cell Senescence*

• DOI: 10.1074/jbc.m110.125138
• 发表时间: 2010-07
• 期刊: The Journal of Biological Chemistry
• 作者: Hong Zhan;Toru Suzuki;K. Aizawa;K. Miyagawa;R. Nagai

The synaptonemal complex protein SYCE2 induces chromosome instability in mitotic cells through activation of the ataxia-telangiectasia-mutated kinase

联会复合体蛋白 SYCE2 通过激活共济失调毛细血管扩张突变激酶诱导有丝分裂细胞染色体不稳定

• 发表时间: 2011
• 作者: Hosoya N;Miyagawa K
• 通讯作者: Miyagawa K

Expression of the meiosis-specific cohesion SMC1beta impairs genomic stability in mitotic cells

减数分裂特异性凝聚 SMC1beta 的表达损害有丝分裂细胞的基因组稳定性

• 发表时间: 2010
• 作者: Goto Y;Hosoya N;Miyagawa K
• 通讯作者: Miyagawa K

The synaptonemal complex protein SYCP3 inhibits the intrinsic homologous recombination pathway in cancer

联会复合体蛋白SYCP3抑制癌症中的内在同源重组途径

• 发表时间: 2010
• 作者: Hosoya N;Miyagawa K
• 通讯作者: Miyagawa K

Involvement of multiple pathways in the generation of aneuploidy caused by defective homologous recombination

多种途径参与由缺陷同源重组引起的非整倍性的产生

• 发表时间: 2010
• 作者: Shiomi T;Boudreault F;Padem N;Higashiyama S;Drazen JM;Tschumperlin DJ.;Miyagawa K
• 通讯作者: Miyagawa K