公开(公告)号：US20150231238A1

公开(公告)日：2015-08-20

申请号：US14004848

申请日：2012-03-15

申请人： Gabriela Garcia ,  William Kubasek ,  Maria Johanna Lahdenranta ,  Gavin MacBeath ,  Charlotte McDonagh ,  Victor Moyo ,  Matthew David Onsum ,  Birgit Schoeberl ,  Mark Sevecka ,  Marisa Wainszelbaum ,  Bo Zhang

发明人： Gabriela Garcia ,  William Kubasek ,  Maria Johanna Lahdenranta ,  Gavin MacBeath ,  Charlotte McDonagh ,  Victor Moyo ,  Matthew David Onsum ,  Birgit Schoeberl ,  Mark Sevecka ,  Marisa Wainszelbaum ,  Bo Zhang

IPC分类号： A61K39/395 ,  A61K45/06 ,  A61K31/138 ,  A61K31/337

CPC分类号： A61K39/39558 ,  A61K31/138 ,  A61K31/337 ,  A61K31/513 ,  A61K31/517 ,  A61K31/7068 ,  A61K33/24 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2039/55 ,  C07K16/2863 ,  C07K16/32 ,  C07K2317/31 ,  C07K2317/73 ,  C07K2317/76 ,  A61K2300/00

摘要： Provided are methods for overcoming resistance to an ErbB pathway inhibitor, such as an EGFR inhibitor or a HER2 inhibitor. The resistance may be acquired resistance to an EGFR inhibitor, such as acquired resistance to gefitinib. In the methods provided, a subject exhibiting resistance to an ErbB pathway inhibitor is selected and both an ErbB 3 inhibitor and a second ErbB pathway inhibitor are administered to the subject, such as an EGFR inhibitor or a HER2 inhibitor. Also provided are methods for inhibiting the growth of a tumor comprising a T790M EGFR mutation by contacting the tumor with an ErbB3 inhibitor and an EGFR inhibitor. Compositions for overcoming resistance to an ErbB pathway inhibitor, comprising both an ErbB 3 inhibitor and a second ErbB pathway inhibitor, such as an EGFR inhibitor or a HER2 inhibitor, are also provided.

摘要翻译： 提供了克服对ErbB途径抑制剂如EGFR抑制剂或HER2抑制剂的抗性的方法。 抗性可能是对EGFR抑制剂的获得性抗性，如对吉非替尼的获得性抗性。 在所提供的方法中，选择表现出对ErbB途径抑制剂的抗性的受试者，并且对受试者，例如EGFR抑制剂或HER2抑制剂施用ErbB 3抑制剂和第二ErbB途径抑制剂。 还提供了通过使肿瘤与ErbB3抑制剂和EGFR抑制剂接触来抑制包含T790M EGFR突变的肿瘤的生长的方法。 还提供了克服对ErbB通路抑制剂的抗性的组合物，其包含ErbB 3抑制剂和第二ErbB途径抑制剂，例如EGFR抑制剂或HER2抑制剂。