首页> 外国专利> DETERMINATION OF CELL SENSITIVITY TO B-Raf INHIBITOR TREATMENT BY DETECTION OF KRAS MUTATION AND RTK EXPRESSION LEVELS

DETERMINATION OF CELL SENSITIVITY TO B-Raf INHIBITOR TREATMENT BY DETECTION OF KRAS MUTATION AND RTK EXPRESSION LEVELS

机译:通过检测KRAS突变和RTK表达水平确定细胞对B-Raf抑制剂的敏感性

摘要

1. A method for identifying a tumor that is not responding to treatment with a B-Raf inhibitor, comprising determining the expression level of receptor tyrosine kinase (RTK) in a sample obtained from a tumor, wherein aberrant expression or induction of said RTK indicates that said patient will not respond to treatment with said a B-Raf inhibitor, and wherein said tumor expresses B-Raf V600E. 2. The method of claim 1, wherein said RTK is EGFR or cMET. 3. The method of claim 2, further comprising identifying said tumor for treatment by administering an effective amount of: (i) an inhibitor of said EGFR or cMET in combination with a B-Raf inhibitor; and (ii) an MEK inhibitor in combination with a B-Raf. 4 inhibitor. The method of claim 3, wherein said RTK is EGFR, further comprising identifying said tumor for treatment by administering an effective amount of: (i) an inhibitor of said EGFR in combination with a B-Raf inhibitor; or (ii) an MEK inhibitor in combination with a B-Raf.5 inhibitor. The method of claim 3, wherein said RTK is cMET, further comprising identifying said tumor for treatment by administering an effective amount of: (i) an inhibitor of said cMET in combination with a B-Raf inhibitor; or (ii) an MEK inhibitor in combination with a B-Raf inhibitor. 6. The method according to claim 3 (i), 4 (i) or 5 (i), wherein said combination is intended for administration in an additional combination with: (a) an MEK inhibitor; or (b) an ERK inhibitor. 7. The method according to any one of paragraphs. 3 or 4, wherein said EGFR inhibitor is erlotinib. 8. The method of claim 7, wherein said combination is intended to be administered in a synergistic amount. The method of claim 1, wherein said type of tumor is colon cancer
机译:1.一种鉴定对B-Raf抑制剂治疗无反应的肿瘤的方法,包括确定从肿瘤获得的样品中受体酪氨酸激酶(RTK)的表达水平,其中所述RTK的异常表达或诱导表明所述患者对使用所述B-Raf抑制剂的治疗无反应,并且其中所述肿瘤表达B-Raf V600E。 2.权利要求1的方法,其中所述RTK是EGFR或cMET。 3.根据权利要求2所述的方法,其进一步包括通过施用有效量的以下物质来鉴定所述肿瘤以进行治疗:(i)所述EGFR或cMET的抑制剂与B-Raf抑制剂的组合; (ii)MEK抑制剂与B-Raf组合。 4抑制剂。 4.根据权利要求3所述的方法,其中所述RTK是EGFR,进一步包括通过施用有效量的以下物质来鉴定所述肿瘤以进行治疗:(i)所述EGFR的抑制剂与B-Raf抑制剂的组合; (ii)MEK抑制剂与B-Raf.5抑制剂组合。 4.根据权利要求3所述的方法,其中所述RTK是cMET,进一步包括通过施用有效量的以下物质来鉴定所述肿瘤以进行治疗:(i)所述cMET的抑制剂与B-Raf抑制剂组合; (ii)MEK抑制剂与B-Raf抑制剂组合。 6.根据权利要求3(i),4(i)或5(i)的方法,其中所述组合旨在与以下的另外的组合一起施用:(a)MEK抑制剂;或(b)ERK抑制剂。 7.根据段落中任一项的方法。 3或4,其中所述EGFR抑制剂是厄洛替尼。 8.权利要求7的方法,其中所述组合旨在以协同量施用。权利要求1的方法,其中所述肿瘤类型是结肠癌

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