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Open AccessReview

Future Therapeutic Directions for Smac-Mimetics

by Emma Morrish 1,2, Gabriela Brumatti 1,2 and John Silke 1,2,*
Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 406;
Received: 21 January 2020 / Revised: 5 February 2020 / Accepted: 7 February 2020 / Published: 11 February 2020
(This article belongs to the Special Issue Inhibitor of Apoptosis Proteins (IAPs) in Cancer Therapy)
It is well accepted that the ability of cancer cells to circumvent the cell death program that untransformed cells are subject to helps promote tumor growth. Strategies designed to reinstate the cell death program in cancer cells have therefore been investigated for decades. Overexpression of members of the Inhibitor of APoptosis (IAP) protein family is one possible mechanism hindering the death of cancer cells. To promote cell death, drugs that mimic natural IAP antagonists, such as second mitochondria-derived activator of caspases (Smac/DIABLO) were developed. Smac-Mimetics (SMs) have entered clinical trials for hematological and solid cancers, unfortunately with variable and limited results so far. This review explores the use of SMs for the treatment of cancer, their potential to synergize with up-coming treatments and, finally, discusses the challenges and optimism facing this strategy.
Keywords: Smac/DIABLO; Smac-Mimetics; IAPs; TNF; cell death; cancer Smac/DIABLO; Smac-Mimetics; IAPs; TNF; cell death; cancer
MDPI and ACS Style

Morrish, E.; Brumatti, G.; Silke, J. Future Therapeutic Directions for Smac-Mimetics. Cells 2020, 9, 406.

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