Fig. 7.

Proposed model for the mechanism by which EGFRi resistance in LUAD is regulated by the CBX5-E2F1-BIRC5 axis. Our findings are consistent with a model wherein loss of CBX5 promotes resistance to EGFRi via E2F1-mediated upregulation of BIRC5 expression, which leads to inhibition of EGFRi-induced apoptosis. CBX5 is down-regulated in EGFRi-resistant cells; however, expression can be restored by treatment with BETi. Consistent with this observation, combined treatment with EGFRi and BETi shows potential therapeutic benefits in cell culture and in a mouse model of EGFRi-resistant LUAD. In addition, similar therapeutic benefits can be achieved by treating EGFRi-resistant cells with a BIRC5 inhibitor.