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Review
. 2016 Feb 25;9(1):11.
doi: 10.3390/ph9010011.

Targeting Cell Survival Proteins for Cancer Cell Death

Manoj K Pandey  1 , Sahdeo Prasad  2 , Amit Kumar Tyagi  3 , Lokesh Deb  4 , Jiamin Huang  5 , Deepkamal N Karelia  6 , Shantu G Amin  7 , Bharat B Aggarwal  8
Affiliations
Review

Targeting Cell Survival Proteins for Cancer Cell Death

Manoj K Pandey et al. Pharmaceuticals (Basel). .

Abstract

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.

Keywords: Bcl-2 family; apoptosis; chemotherapeutics; nutraceuticals; survival proteins; surviving.

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Figures

Figure 1
Figure 1
Survival family members associated with regulation of apoptosis. Abbreviations: Mcl-1, myeloid cell leukemia 1; Bcl-xL, B-cell lymphoma-extra-large; Bcl-2, B-cell CLL/lymphoma 2; Bcl-w, Bcl-2 like 2; BIM, Bcl-2 interacting protein; BIK, Bcl-2 interacting killer; BAD, Bcl-2 antagonist of cell death; BID, BH3 interacting domain death agonist; NOXA, Phorbol-12-myristate-13-acetate-induced protein 1; PUMA, p53 upregulated modulator of apoptosis; HRK, harakiri; BOK, Bcl-2 related ovarian killer; BAK, Bcl-2 antagonist killer1; BAX, Bcl-2 associated X protein; IAPs, Inhibitors of apoptosis; HSP, heat-shock protein.
Figure 2
Figure 2
Chemical structure of survival family protein inhibitors.
Figure 2
Figure 2
Chemical structure of survival family protein inhibitors.
Figure 2
Figure 2
Chemical structure of survival family protein inhibitors.
Figure 2
Figure 2
Chemical structure of survival family protein inhibitors.
See this image and copyright information in PMC

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