期刊
CLINICAL & TRANSLATIONAL ONCOLOGY
卷 10, 期 6, 页码 318-323出版社
SPRINGER-VERLAG ITALIA SRL
DOI: 10.1007/s12094-008-0207-8
关键词
PARP-1; carcinogenesis; DNA repair; antineoplasic therapy
类别
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 recombination-deficient 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.
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