Poly(ADP-ribose)polymerase-1 (PARP-1) in carcinogenesis: potential role of PARP inhibitors in cancer treatment
Clin. transl. oncol. (Print)
; 10(6): 318-323, jun. 2008. ilus, tab
Article
in English
| IBECS
| ID: ibc-123455
Responsible library:
ES1.1
Localization: BNCS
ABSTRACT
Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear, zinc-finger, deoxyribonucleic acid (DNA)-binding protein that detects specifically DNA strand breaks generated by different genotoxic agents. Whereas activation of PARP-1 by mild genotoxic stimuli facilitates DNA repair and cell survival, severe DNA damage triggers different pathways of cell death, including PARP-mediated cell death through the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus. Pharmacological inhibition or genetic ablation of PARP-1 results in a clear benefit in cancer treatment by different mechanisms, including selective killing of homologous recombinationdeficient tumor cells, downregulation of tumor-related gene expression, and decrease in the apoptotic threshold in the cotreatment with chemo- and radiotherapy. We summarize in this review the findings and concepts for the role of PARP-1 and poly(ADP-ribosylation) in the regulation of carcinogenesis and some of the preclinical and clinical data available for these agents, together with the challenges facing the clinical development of these agents (AU)
RESUMEN
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Collection:
National databases
/
Spain
Database:
IBECS
Main subject:
Clinical Trials as Topic
/
Poly(ADP-ribose) Polymerases
/
Enzyme Inhibitors
/
Neoplasms
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Clin. transl. oncol. (Print)
Year:
2008
Document type:
Article
Institution/Affiliation country:
Instituto de Parasitología y Biomedicina López Neyra/Spain