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 journalArticle

107 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Inhibitor of Apoptosis Proteins
Neoplasms
Nodal Protein
Drug Therapy
Caspases
Cell Division
Cell Survival
Histology
Vaccination
Cell Death
Monoclonal Antibodies
Clinical Trials
Radiation
Apoptosis
Recurrence
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

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

Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin. / Kelly, Ronan J.; Lopez-Chavez, Ariel; Citrin, Deborah; Janik, John E.; Morris, John C.

In: Molecular Cancer, Vol. 10, 35, 06.04.2011.

Research output: Contribution to journalArticle

Kelly, Ronan J. ; Lopez-Chavez, Ariel ; Citrin, Deborah ; Janik, John E. ; Morris, John C. / Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin. In: Molecular Cancer. 2011 ; Vol. 10.
@article{9dd478d271c44cedbb54ff3d7efa777b,
title = "Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin",
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.",
author = "Kelly, {Ronan J.} and Ariel Lopez-Chavez and Deborah Citrin and Janik, {John E.} and Morris, {John C.}",
year = "2011",
month = "4",
day = "6",
doi = "10.1186/1476-4598-10-35",
language = "English (US)",
volume = "10",
journal = "Molecular Cancer",
issn = "1476-4598",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin

AU - Kelly, Ronan J.

AU - Lopez-Chavez, Ariel

AU - Citrin, Deborah

AU - Janik, John E.

AU - Morris, John C.

PY - 2011/4/6

Y1 - 2011/4/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79953655787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953655787&partnerID=8YFLogxK

U2 - 10.1186/1476-4598-10-35

DO - 10.1186/1476-4598-10-35

M3 - Article

C2 - 21470426

AN - SCOPUS:79953655787

VL - 10

JO - Molecular Cancer

JF - Molecular Cancer

SN - 1476-4598

M1 - 35

ER -