The development of molecular targeted therapy has improved clinical outcomes in patients with life-threatening advanced lung cancers with driver oncogenes. However, selective treatment for KRAS -mutant lung cancer remains underdeveloped. We have successfully characterised specific molecular and pathological features of KRAS -mutant lung cancer utilising newly developed cell line models that can elucidate the differences in driver oncogenes among tissues with identical genetic backgrounds. Among these KRAS -mutation-associated specific features, we focused on the IGF2-IGF1R pathway, which has been implicated in the drug resistance mechanisms to AMG 510, a recently developed selective inhibitor of KRAS G12C lung cancer. Experimental data derived from our cell line model can be used as a tool for clinical treatment strategy development through understanding of the biology of lung cancer. The model developed in this paper may help understand the mechanism of anticancer drug resistance in KRAS -mutated lung cancer and help develop new targeted therapies to treat patients with this disease. • To compare the characteristics of driver oncogenes in the same genetic background, they were transduced in BEAS2B cells. • BEAS2B- KRAS- G12C cells demonstrated aggressive phenotype compared with BEAS2B cells with EGFR-L858R or EML4-ALK. • AMG 510 synergised with linsitinib in BEAS2B- KRAS- G12C and KRAS G12C-mutated lung cancer cells. • Our cell line model may help understand anticancer drug resistance in KRAS -mutated lung cancer. [ABSTRACT FROM AUTHOR]