Supplementary Figures includes 6 figures. Supplementary Figure S1: Bypass pathway activation detected using a protein array confers resistance in PC9 cells. Supplementary Figure S2: IGF2-IGF1R activation contributes to acquired resistance to osimertinib in PC9AZDR cells. Supplementary Figure S3: Elucidation of MET amplification as a resistant mechanism in KOLK17 and KOLK37 cells. Supplementary Figure S4: IGF2-IGF1R bypass pathway contributes to acquired resistance in osimertinib-resistant PDCs. Supplementary Figure S5: Quantities of IGF2 reduce in a drug-free medium in KOLK43 cells. Supplementary Figure S6: Effect of combination therapy in vivo.