Our findings presented in this report suggest that overexpression of DARPP-32 isoforms in EGFR-mutated NSCLC promotes EGFR:ERBB3 “bypass signaling” that enables tumor cells to evade EGFR TKI monotherapy-induced apoptosis by potentiating oncogenic AKT and ERK signaling. Here, EGFR is linked to non-small cell lung carcinoma.