Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin.
Mol Cancer
; 10: 35, 2011 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-21470426
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Proteínas Reguladoras de Apoptose
/
Proteínas Inibidoras de Apoptose
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos