公开(公告)号：EP3204514A1

公开(公告)日：2017-08-16

申请号：EP15790296.6

申请日：2015-10-09

申请人： Daiichi Sankyo Co., Ltd.

发明人： TSE, Ngai-chiu Archie ,  NAKAMARU, Kenji ,  TAZAKI, Koichi ,  WATANABE, Kenji ,  SEKI, Takahiko

IPC分类号： C12Q1/68 ,  A61K31/499

CPC分类号： C12Q1/6886 ,  A61K31/4439 ,  A61K31/499 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158 ,  G01N33/574

摘要： Provided are gene signatures that are predictive of the sensitivity of a cancer or tumor to an MDM2i or an antagonist of the MDM2-p53 interaction. Differentially expressed genes in the provided gene signatures serve as biomarkers for determining and assessing the sensitivity of cancer and tumor samples to treatment or therapy with an MDM2i. Also provided are methods of determining MDM2i sensitivity of a test sample such as different cancer and tumor types and subtypes, based on the expression of genes in the MDM2i sensitive gene signatures in reference samples and the test sample even if all of the MDM2i sensitivities of the reference samples are unknown, and treating individuals with an MDM2i if their cancers are determined to be MDM2i-sensitive, based on the practice of the described methods. TP53 gene and p53 protein status can also be determined for the samples undergoing analysis for MDM2i sensitivity.

摘要翻译： 提供可预测癌症或肿瘤对MDM2i或MDM2-p53相互作用拮抗剂敏感性的基因标记。 所提供的基因标记中的差异表达基因充当用于确定和评估癌症和肿瘤样品对用MDM2i治疗或治疗的敏感性的生物标志物。 还提供了基于参考样品和测试样品中MDM2i敏感性基因标签中的基因表达来确定测试样品（例如不同癌症和肿瘤类型和亚型）的MDM2i敏感性的方法，即使所有MDM2i敏感性 参考样本是未知的，并且基于所描述的方法的实践，如果MDM2i的癌症被确定为MDM2i敏感的，则用MDM2i治疗个体。 对于MDM2i敏感性分析的样品，也可以确定TP53基因和p53蛋白的状态。 本发明的方法，平台，试剂盒，试剂和组合物提供了用于个体化或个体化治疗其癌症对MDM2抑制剂显示敏感性的有利方法和工具，如通过基因标记中的基因相对于对照 到所描述的方法。