The role of inhibitors of poly(ADP-ribose) polymerase as resistance-modifying agents in cancer therapy

Poly(ADP-ribose) polymerase (PARP) plays an important role in a number of cellular processes including DNA repair. Since poly(ADP-ribosyl)ation occurs in response to radiation- or drag-induced DNA damage, inhibitors of the enzyme may enhance the antitumour activity of radiotherapy or cytotoxic drug...

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Bibliographic Details
Published in:Biochimie 1995, Vol.77 (6), p.408-422
Main Authors: Griffin, R.J., Curtin, N.J., Newell, D.R., Golding, B.T., Durkacz, B.W., Calvert, A.H.
Format: Article
Language:English
Subjects:
Animals
cancer therapy
DNA Repair - drug effects
Drug Resistance, Neoplasm
Drug Synergism
Enzyme Inhibitors - therapeutic use
Humans
inhibitors
Molecular Structure
Neoplasms - drug therapy
Neoplasms - radiotherapy
Neoplasms - therapy
poly(ADP-ribose) polymerase
Poly(ADP-ribose) Polymerase Inhibitors
radiopotentiation
resistance-modifying agents
Structure-Activity Relationship
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Summary:Poly(ADP-ribose) polymerase (PARP) plays an important role in a number of cellular processes including DNA repair. Since poly(ADP-ribosyl)ation occurs in response to radiation- or drag-induced DNA damage, inhibitors of the enzyme may enhance the antitumour activity of radiotherapy or cytotoxic drug treatment. In this review the development of PARP inhibitors is discussed, and structure-activity relationships amongst inhibitors of the enzyme are presented. Studies to date regarding the in vitro and in vivo activity of PARP inhibitors, as resistance modifying agents in cancer therapy, are also overviewed.
ISSN:0300-9084
1638-6183
DOI:10.1016/0300-9084(96)88154-5