Survivin, a cancer target with an emerging role in normal adult tissues.
Survivin, an inhibitor of apoptosis protein, is highly expressed in most cancers and associated with chemotherapy resistance, increased tumor recurrence, and shorter patient survival, making antisurvivin therapy an attractive cancer treatment strategy. However, growing evidence indicates that survivin is expressed in normal adult cells, particularly primitive hematopoietic cells, T lymphocytes, polymorphonuclear neutrophils, and vascular endothelial cells, and may regulate their proliferation or survival. In preclinical animal models, targeted antisurvivin therapies show efficacy without overt toxicity. However, consequences of prolonged survivin disruption in normal cells, particularly those associated with continuous renewal, have not been clearly determined. Understanding the role of survivin in normal versus malignant cells will be important in identifying strategies that maximally disrupt survivin in cancer cells with minimal effect on normal tissues. In this review, we summarize the prognostic relevance of survivin in cancer that justifies the pursuit of antisurvivin therapies and discuss differences in survivin expression between normal and cancer cells. We subsequently review expression of survivin in normal adult tissues and evaluate preclinical antisurvivin therapies reported to date in light of emerging roles for survivin in normal physiology, particularly hematopoiesis, angiogenesis, and immune function.
Fukuda
Seiji
S
Walther Oncology Center, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202, USA. lpelus@iupui.edu
Pelus
Louis M
LM
D000328:Adult; D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007109:Immunity; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D000077022:Survivin
C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin