Expression data from MDA-MB-231 parental and xenograft tumor cells treated with Smac mimetic SM-164.

Small-molecule Smac mimetics target inhibitor of apoptosis (IAP) proteins to induce TNF-dependent apoptosis in cancer cells and several Smac mimetics have been advanced into clinical development as a new class of anticancer drugs. However, preclinical studies have shown that only a small subset of cancer cell lines are sensitive to Smac mimetics used as single agents and these cell lines are at risk of developing drug resistance to Smac mimetics. Thus, it is important to understand the molecular mechanisms underlying intrinsic and acquired resistance of cancer cells to Smac mimetics in order to develop effective therapeutic strategies to overcome or prevent Smac mimetic resistance.

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Bai L, McEachern D, Yang CY, Lu J, Sun H, Wang S