Survivin: a new target for anti-cancer therapy.
Survivin is one of the most cancer-specific proteins identified to date, being upregulated in almost all human tumors. Biologically, survivin has been shown to inhibit apoptosis, enhance proliferation and promote angiogenesis. Because of its upregulation in malignancy and its key role in apoptosis, proliferation and angiogenesis, survivin is currently attracting considerable attention as a new target for anti-cancer therapies. In several animal model systems, downregulation of survivin or inactivation of its function has been shown to inhibit tumor growth. Strategies under investigation to target survivin include antisense oligonucleotides, siRNA, ribozymes, immunotherapy and small molecular weight molecules. The translation of these findings to the clinic is currently ongoing with a number of phase I/II clinical trials targeting survivin in progress. These include use of the antisense oligonucleotide LY2181308, the low molecular weight molecule inhibitor YM155 and survivin-directed autologous cytotoxic T lymphocytes. The optimum use of survivin antagonists in the treatment of cancer is likely to be in combination with conventional cancer therapies.
Ryan
Bríd M
BM
Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4258, USA. ryanb@mail.nih.gov
O'Donovan
Norma
N
Duffy
Michael J
MJ
D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin