Mcl-1 as a "barrier" in cancer treatment: Can we target it now?

摘要: During the last two decades, study of Mcl-1, an anti-apoptotic member Bcl-2 family, attracted researchers due to its important role in cancer cell survival and tumor development. The significance Mcl-1 protein resistance chemotherapeutics makes it attractive target therapy. Here, we discuss diverse possibilities for indirect inhibition through downregulation, example, via targeting proteasomal degradation or blockage translation transcription. We also provide overview direct blocking protein-protein interactions with pro-apoptotic family proteins, including examples most promising regulators selective BH3-mimetics, which at present are under clinical evaluation. Moreover, several approaches co-targeting other proteins (e.g., CDKs) presented. In addition, highlight broad spectrum problems that accompanied discovery development effective inhibitors.