The invention relates to pharmaceutical compositions for and methods of treatment with HER3-targeted combination therapy. The invention relates to pharmaceutical compositions comprising an oligomer which targets HER3 (and optionally one or more of HER2 and EGFR) mRNA in a cell, leading to reduced expression of HER3 and optionally HER2 and/or EGFR, and a small molecule protein tyrosine kinase inhibitor of one or more receptor tyrosine kinases, leading to inhibition of signaling and/or internalization of receptor dimers into the cell. The combination therapy is beneficial for a range of medical disorders, such hyperproliferative disorders (e.g., cancer). The invention provides methods of treating hyperproliferative disorders with a combination of an oligomer and a protein tyrosine kinase inhibitor.
