Survivin (BIRC5), a member of the
inhibitor of apoptosis protein (IAP) family that inhibits
caspases and blocks cell death is highly expressed in
cancer and is associated with a poorer clinical outcome. Functioning simultaneously during cell division and apoptosis inhibition,
survivin plays a pivotal role in determining cell survival.
Survivin has consistently been identified by molecular profiling analysis to be associated with higher
tumor grade, more advanced disease, abbreviated survival, accelerated rates of recurrence, and
chemotherapy and radiation resistance.
Survivin's differential expression in
cancer compared to normal tissue and its role as a
nodal protein in a number of cellular pathways make it a highly flexible therapeutic target, suitable for small-molecule inhibitiors, molecular antagonists, and vaccination-based
therapies. By targeting
survivin it is hoped that multiple
tumor signaling circuitries may be simultaneously disabled. This effect may be applicable to many
tumor histologies irrespective of specific genetic makeup. To date,
survivin inhibitors have shown modest activity as single agents, but it is anticipated that when given in combination with cytotoxic
chemotherapy or
monoclonal antibodies they may exhibit enhanced efficacy. This review discusses the complex circuitry of
survivin in human
cancers and highlights clinical trials involving novel agents that target this important
protein.