Publication:
A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer.

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Date

2022-03-23

Authors

Cetraro, Pierina
Plaza-Diaz, Julio
MacKenzie, Alex
Abadia-Molina, Francisco

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MDPI AG
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Abstract

The Inhibitor of Apoptosis (IAP) family possesses the ability to inhibit programmed cell death through different mechanisms; additionally, some of its members have emerged as important regulators of the immune response. Both direct and indirect activity on caspases or the modulation of survival pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), have been implicated in mediating its effects. As a result, abnormal expression of inhibitor apoptosis proteins (IAPs) can lead to dysregulated apoptosis promoting the development of different pathologies. In several cancer types IAPs are overexpressed, while their natural antagonist, the second mitochondrial-derived activator of caspases (Smac), appears to be downregulated, potentially contributing to the acquisition of resistance to traditional therapy. Recently developed Smac mimetics counteract IAP activity and show promise in the re-sensitization to apoptosis in cancer cells. Given the modest impact of Smac mimetics when used as a monotherapy, pairing of these compounds with other treatment modalities is increasingly being explored. Modulation of molecules such as tumor necrosis factor-α (TNF-α) present in the tumor microenvironment have been suggested to contribute to putative therapeutic efficacy of IAP inhibition, although published results do not show this consistently underlining the complex interaction between IAPs and cancer.

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MeSH Terms

Inhibitor of Apoptosis Proteins
Caspases
Tumor Microenvironment
Neoplasms
Apoptosis
Tumor Necrosis Factor-alpha
Immunity

DeCS Terms

Apoptosis
Caspasas
Apoptosis
Caspasas
Factor de necrosis tumoral alfa
Inmunidad
Microambiente tumoral
Neoplasias
Proteínas inhibidoras de la apoptosis

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Keywords

NF-κB, SMAC mimetics, TNF-α, apoptosis, endoplasmic reticulum stress, inhibitor of apoptosis proteins

Citation

Cetraro P, Plaza-Diaz J, MacKenzie A, Abadía-Molina F. A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer. Cancers (Basel). 2022 Mar 25;14(7):1671