Understanding of the pharmacological responses to drug treatment in cancer cells is essential for discovery and development of novel anticancer therapies. In this study, drug resistant cell lines, HCC827-BR1 and HCC827-BR2, were developed by treatment of HCC827 cells with escalating concentration of afatinib (BIBW2992). The CC50 of BIBW2992 in HCC827 ranges from 2 to 10 nM while the CC50s of BIBW2992 in HCC827-BR1 and HCC827-BR2 are approximately 10 uM. Gene expression analysis revealed that the epithelial-mesenchymal transition (EMT) may be involved in resistance to BIBW2992. The drug-resistant cells are more invasive as evaluated under in vitro assays. Results from this study have also identified that the drug-resistance cells are more sensitive to another kinase inhibitor; indicating that an oncogenic shift has occurred. When this drug is combined with BIBW2992 in treatment of HCC827 cells, much less colonies survived compared to cells treated by BIBW2992 alone. The clinical ramifications of these observations will be discussed.
