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.