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.
