Taken together with our in vitro findings, our results indicate that DARPP-32 isoforms promote EGFR TKI-refractory NSCLC cell survival by stimulating the formation of active EGFR and ERBB3 heterodimers, increased AKT and ERK activation, and evasion of EGFR TKI-dependent apoptosis. Here, EGFR is linked to non-small cell lung carcinoma.