Venetoclax (ABT-199) and idasanutlin (RG7388) are efficient anticancer drugs 
targeting two essential apoptosis markers, Bcl-2 and MDM2, respectively. Recent 
studies have shown that the combination of these two drugs leads to remarkable 
enhancement of anticancer efficacy, both in vitro and in vivo. In an attempt to 
disclose the relationships of their protein targets, competitive affinity-based 
proteome profiling coupled with bioimaging was employed to characterize their 
protein targets in the same cancer cell line and tumor tissue. A series of 
protein hits, including ITPR1, GSR, RER1, PDIA3, Apoa1, and Tnfrsf17 were 
simultaneously identified by pull-down/LC-MS/MS with the two sets of 
affinity-based probes. Dual imaging was successfully carried out, with the 
simultaneous detection of Bcl-2 and MDM2 expression in various cancer cells. 
This could facilitate the novel diagnostic and therapeutic strategies of dual 
targeting of Bcl-2/MDM2.