2. Academic Validation
  3. Future Therapeutic Directions for Smac-Mimetics

Future Therapeutic Directions for Smac-Mimetics

  • Cells. 2020 Feb 11;9(2):406. doi: 10.3390/cells9020406.
Emma Morrish 1 2,  Gabriela Brumatti 1 2,  John Silke 1 2
Affiliations

Affiliations

  • 1 Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia.
  • 2 Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.
PMID: 32053868 DOI: 10.3390/cells9020406
Abstract

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

IAPs; Smac-Mimetics; Smac/DIABLO; TNF; cancer; cell death.

Figures