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    • 4. 发明申请
    • METHOD OF PREDICTING AND REDUCING RISK OF METASTASIS OF BREAST CANCER TO LUNG
    • 预防和降低乳腺癌转移至肺癌的风险的方法
    • WO2006074367A2
    • 2006-07-13
    • PCT/US2006/000461
    • 2006-01-05
    • SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCHMASSAGUE, JoanGUPTA, Gaorav, PMINN, Andy
    • MASSAGUE, JoanGUPTA, Gaorav, PMINN, Andy
    • C12N15/1137C12N15/1136C12N2310/14C12Y114/99001
    • A signature for breast cancer tissue derived from a patient is established that is indicative of the virulence and risk of lung metastasis by determining the expression levels to define a sample signature, and comparing this sample signature to a reference signature. The reference signature defines a standard expression level for each gene and a significant change direction, i.e., either overexpressed or underexpressed. A sample signature that differs from the reference signature in the significant change direction for a predetermined number of the genes tested is indicative of a significant risk of lung metastasis. This determination is used to define appropriate treatment and monitoring options for the patient. Risk of metastasis to the lung can be reduced by treatment with a therapeutic combination that either (1) contains a first agent effective to inhibit epiregulin activity and a second agent effective to inhibit activity of a protein selected from the group consisting of MMPl, MMP2 and PTGS2, or (2) contains a therapeutic agent or combination of agents effective to inhibit activity MMPl, MMP2 and PTGS2. Agents that inhibit the CXCLl pathway also can be used individually or in combination with these combinations.
    • 通过确定表达水平来确定样品标记,并将该样本标记与参考标记进行比较,建立了从患者衍生的乳腺癌组织的特征,其指示肺转移的毒力和风险。 参考标记定义每个基因的标准表达水平和显着改变方向,即过表达或低表达。 对于预定数量的所测试的基因,在显着改变方向上与参考标记不同的样本标记指示肺转移的显着风险。 该确定用于为患者定义适当的治疗和监测选项。 可以通过用(1)含有有效抑制去甲孕腺素活性的第一药剂和有效抑制选自下组的蛋白质的第二药剂的治疗组合来治疗肺转移的风险:MMP1,MMP2和 PTGS2或(2)含有治疗剂或有效抑制MMP1,MMP2和PTGS2活性的药剂组合。 抑制CXCL1途径的药剂也可以单独使用或与这些组合组合使用。