We next determined the underlying mechanism for the unexpected trend in tumor uptake of the blocked cohorts. Pathological analysis revealed an increase in EGFR (Fig. 4C, top) and HER3 (Fig. 4C, bottom) staining in both EGFR and HER3 blocked BxPC-3 tumors compared to control. From the western blots, cetuximab-treated AsPC-1 exhibited a two-fold decrease in total EGFR protein, coupled with a 1.3-fold increase in HER3 as shown by densitometry (Fig. 4D). With the DL3.6b blocked AsPC-1 tumors, a 2.25-fold increase in EGFR with a concomitant three-fold decrease in HER3 was displayed. Similar trends were observed in BxPC-3 wherein cetuximab-blocked groups displayed suppressed EGFR and HER3 (Fig. 4D). Saturation of the HER3 sites exhibited a moderate increase in EGFR expression, coupled with a decrease in HER3. These results imply that the blocking dose of antibody (cetuximab or DL3.6b) may be inducing an upregulation of either receptor in an attempt to maintain proliferation.