Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin

Ronan J. Kelly, Ariel Lopez-Chavez, Deborah Citrin, John E. Janik, John C. Morris

Research output: Contribution to journalReview article

115 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number35
JournalMolecular Cancer
Volume10
DOIs
StatePublished - Apr 6 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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    Kelly, R. J., Lopez-Chavez, A., Citrin, D., Janik, J. E., & Morris, J. C. (2011). Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin. Molecular Cancer, 10, [35]. https://doi.org/10.1186/1476-4598-10-35