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The IAP Protein Family, SMAC Mimetics and Cancer Treatment
1R. E. Kavetsky Institute of Experimental Pathology, Oncology & Radiobiology Kyiv, Ukraine.
Critical Reviews in Oncogenesis
|December 6, 2016
Summary
Inhibitor of apoptosis proteins (IAPs) are key cancer targets. SMAC mimetics, like birinapant, offer new anticancer therapies by blocking IAPs, with ongoing clinical trials evaluating their effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Acquired resistance to apoptosis is a hallmark of cancer.
- Inhibitor of Apoptosis Proteins (IAPs) regulate cell death and other functions.
- IAPs are promising targets for anticancer drug development.
Purpose of the Study:
- To review the background of IAP proteins and their antiapoptotic mechanisms.
- To focus on the development of SMAC mimetics as IAP antagonists.
- To introduce specific SMAC mimetics and their clinical trials.
Main Methods:
- Review of existing literature on IAP proteins and SMAC mimetics.
- Analysis of mechanisms of IAP antiapoptotic activity.
- Overview of clinical trial data for SMAC mimetics (birinapant, LCL161, DEBIO1143/AT-406).
Main Results:
- IAPs possess antiapoptotic activities and regulate cell functions.
- SMAC mimetics are synthetic IAP antagonists under development.
- Clinical trials are evaluating SMAC mimetics as therapeutics.
Conclusions:
- SMAC mimetics represent a promising therapeutic strategy against cancer.
- Further research is needed to identify biomarkers for SMAC mimetic efficacy.
- Biomarkers may include caspases and TNFα pathway factors.
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