The inhibitors of apoptosis (IAPs) as cancer targets
Abstract
Apoptosis has been accepted as a fundamental component in the pathogenesis of cancer, in addition to other human diseases including neurodegeneration, coronary disease and diabetes. The origin of cancer involves deregulated cellular proliferation and the suppression of apoptotic processes, ultimately leading to tumor establishment and growth. Several lines of evidence point toward the IAP family of proteins playing a role in oncogenesis, via their effective suppression of apoptosis. The central mechanisms of IAP apoptotic suppression appear to be through direct caspase and pro-caspase inhibition (primarily caspase 3 and 7) and modulation of, and by, the transcription factor NF-kappaB. Thus, when the IAPs are over-expressed or over-active, as is the case in many cancers, cells are no longer able to die in a physiologically programmed fashion and become increasingly resistant to standard chemo- and radiation therapies. To date several approaches have been taken to target and eliminate IAP function in an attempt to re-establish sensitivity, reduce toxicity, and improve efficacy of cancer treatment. In this review, we address IAP proteins as therapeutic targets for the treatment of cancer and emphasize the importance of novel therapeutic approaches for cancer therapy. Novel targets of IAP function are being identified and include gene therapy strategies and small molecule inhibitors that are based on endogenous IAP antagonists. As well, molecular mechanistic approaches, such as RNAi to deplete IAP expression, are in development.
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Apoptosis protein inhibitors (IAPs), such as XIAP, C-IAP1, C-IAP2, are a crucial class of endogenous anti-apoptosis proteins.
“Apoptosis protein inhibitors (IAPs), such as XIAP, C-IAP1, C-IAP2, are a crucial class of endogenous anti-apoptosis proteins.453,454”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [454]
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- Authors
- Hunter, A. M., LaCasse, E. C., & Korneluk, R. G.
- Affiliations
- University of Ottawa (CA)
- Children's Hospital of Eastern Ontario (CA)
- Corresponding author
- Korneluk, Robert G.
- Venue
- Apoptosis
- Published
- 2007-06-19
- Volume
- 12
- Issue
- 9
- Pages
- 1543-1568
- ISSN
- 1360-8185 (ISSN-L)
- 1573-675X
- OpenAlex
- W2008181517
- Cited by
- 565
- References
- 4
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 16 · 2023: 13 · 2022: 14 · 2021: 21 · 2020: 20 · 2019: 20 · 2018: 32 · 2017: 35 · 2016: 27 · 2015: 38 · 2014: 35 · 2013: 36 · 2012: 44
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- APOPTOSIS (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- inhibitor of apoptosis proteins, IAP proteins, cancer therapy, caspase inhibition, caspase-3, caspase-7, NF-κB, chemoresistance, radioresistance (biology), IAP antagonists, small molecule inhibitors, gene therapy, RNA interference, therapeutic target
- MeSH terms
- Checkpoint Kinase 1, High-Temperature Requirement A Serine Peptidase 2, Survivin, Animals, Enzyme Activation, Genetic Vectors, Humans, Microtubule-Associated Proteins, Neoplasm Proteins, Neoplasms, Peptide Termination Factors, Protein Kinases, Serine Endopeptidases, Oligonucleotides, Antisense, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Caspases, Mitochondrial Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Inhibitor of Apoptosis Proteins, X-Linked Inhibitor of Apoptosis Protein, Caspase Inhibitors
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