title: Targeting Cell Survival Proteins for Cancer Cell Death.
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.
authors.affiliation: Department of Pharmacology, College of Medicine, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, USA. mkp13@psu.edu.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Pandey
authors.affiliation: Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. sprasad@mdanderson.org.
authors.forename: Sahdeo
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. amittyagiiitd@gmail.com.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Tyagi
authors.affiliation: Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. lokeshdeb.ibsd@nic.in.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Deb
authors.affiliation: Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. zshuangjiamin@126.com.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, College of Medicine, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, USA. dkarelia@hmc.psu.edu.
authors.forename: Deepkamal N
authors.initials: DN
authors.lastname: Karelia
authors.affiliation: Department of Pharmacology, College of Medicine, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, USA. sga3@psu.edu.
authors.forename: Shantu G
authors.initials: SG
authors.lastname: Amin
authors.affiliation: Department of Experimental Therapeutics, Cytokine Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. bbaggarwa@gmail.com.
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
keywords: Bcl-2 family; apoptosis; chemotherapeutics; nutraceuticals; survival proteins; surviving