Receptor tyrosine kinases are implicated in resistance to treatment with their blockade stimulating compensatory pathways to rescue signaling activity. Recent studies reported that antagonism of EGFR resulted in the induction of other compensatory pathways such as the human epidermal receptor 3 (HER3) receptor8–10. HER3 amplification in solid tumors is associated with poor survival and resistance to therapy11. For example, cetuximab treatment demonstrated increased HER3 in colon12, head and neck13 and triple negative breast cancer14. In PDAC, HER3 is the preferred dimerization partner of EGFR15 with its concomitant activation rendering this malignancy impervious to EGFR and HER2 targeted therapy5. Furthermore, EGFR and HER3 are highly expressed in PDAC, marking this aggressive disease with poor survival rates5,6.