Broad targeting of resistance to apoptosis in cancer
- PMID: 25936818
- PMCID: PMC4720504
- DOI: 10.1016/j.semcancer.2015.03.001
Broad targeting of resistance to apoptosis in cancer
Abstract
Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer.
Keywords: Apoptosis; Apoptosis evasion; Autophagy; Necrosis; Nuclear transporters, natural chemopreventive agents.
Copyright © 2015 Elsevier Ltd. All rights reserved.
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References
-
- Ringash J, Au HJ, Siu LL, Shapiro JD, Jonker DJ, Zalcberg JR, et al. Quality of life in patients with K-RAS wild-type colorectal cancer: the CO.20 phase 3 randomized trial. Cancer. 2014;120:181–9. - PubMed
-
- Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74. - PubMed
-
- Du TA. Cell death: balance through a bivalent regulator. Nat Rev Mol Cell Biol. 2013;14:546. - PubMed
-
- Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN. Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 1993;4:327–32. - PubMed
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