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Targeting Cell Survival Proteins for Cancer Cell Death

Department of Pharmacology, College of Medicine, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, USA
Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Author to whom correspondence should be addressed.
Academic Editors: Ashkan Emadi and Dhimant Desai
Pharmaceuticals 2016, 9(1), 11;
Received: 3 December 2015 / Revised: 8 February 2016 / Accepted: 16 February 2016 / Published: 25 February 2016
(This article belongs to the Special Issue Chemotherapeutic Agents)
Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein (HSP) families. The aberrant expression of these proteins is associated with a range of biological activities that promote cancer cell survival, proliferation, and resistance to therapy. Several therapeutic strategies that target survival proteins are based on mimicking BH3 domains or the IAP-binding motif or competing with ATP for the Hsp90 ATP-binding pocket. Alternative strategies, including use of nutraceuticals, transcriptional repression, and antisense oligonucleotides, provide options to target survival proteins. This review focuses on the role of survival proteins in chemoresistance and current therapeutic strategies in preclinical or clinical trials that target survival protein signaling pathways. Recent approaches to target survival proteins-including nutraceuticals, small-molecule inhibitors, peptides, and Bcl-2-specific mimetic are explored. Therapeutic inventions targeting survival proteins are promising strategies to inhibit cancer cell survival and chemoresistance. However, complete eradication of resistance is a distant dream. For a successful clinical outcome, pretreatment with novel survival protein inhibitors alone or in combination with conventional therapies holds great promise. View Full-Text
Keywords: apoptosis; survival proteins; chemotherapeutics; nutraceuticals; Bcl-2 family; surviving apoptosis; survival proteins; chemotherapeutics; nutraceuticals; Bcl-2 family; surviving
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MDPI and ACS Style

Pandey, M.K.; Prasad, S.; Tyagi, A.K.; Deb, L.; Huang, J.; Karelia, D.N.; Amin, S.G.; Aggarwal, B.B. Targeting Cell Survival Proteins for Cancer Cell Death. Pharmaceuticals 2016, 9, 11.

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