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Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs)
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Journal Article
Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs)
2017
Overview
Inhibitors of apoptosis (IAPs) are a family of proteins that play a significant role in the control of programmed cell death (PCD). PCD is essential to maintain healthy cell turnover within tissue but also to fight disease or infection. Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression. Therefore, it is unsurprising that cancer cells demonstrate significantly elevated expression levels of IAPs, resulting in improved cell survival, enhanced tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has garnered substantial scientific interest and as resistance to anti-cancer agents becomes more prevalent, targeting IAPs has become an increasingly attractive strategy to re-sensitize cancer cells to chemotherapies, antibody based-therapies and TRAIL therapy. Antagonism strategies to modulate the actions of XIAP, cIAP1/2 and survivin are the central focus of current research and this review highlights advances within this field with particular emphasis upon the development and specificity of second mitochondria-derived activator of caspase (SMAC) mimetics (synthetic analogs of endogenously expressed inhibitors of IAPs SMAC/DIABLO). While we highlight the potential of SMAC mimetics as effective single agent or combinatory therapies to treat cancer we also discuss the likely clinical implications of resistance to SMAC mimetic therapy, occasionally observed in cancer cell lines.
Publisher
Springer US,Springer,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Cancer
/ Caspase
/ Drug Resistance, Neoplasm - genetics
/ Humans
/ Inhibitor of Apoptosis Proteins - antagonists & inhibitors
/ Inhibitor of Apoptosis Proteins - genetics
/ Intracellular Signaling Peptides and Proteins - antagonists & inhibitors
/ Intracellular Signaling Peptides and Proteins - genetics
/ Mitochondrial Proteins - antagonists & inhibitors
/ Mitochondrial Proteins - genetics
/ Oncology
/ Proteins
/ Review
/ Survival
/ Survivin
/ TNF-Related Apoptosis-Inducing Ligand - genetics
/ Virology
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