Clinical perspectives of PARP inhibitors

Grazia Graziani, Csaba Szabo

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Poly(ADP-ribose) polymerase (PARP) activation plays a role in the pathogenesis of various cardiovascular and inflammatory diseases. At the same time, PARP activation is also relevant for the ability of cells to repair injured DNA. Thus, depending on the circumstances, pharmacological inhibitors of PARP may be able to attenuate ischemic and inflammatory cell and organ injury or may be able to enhance the cytotoxicity of antitumor agents. Both aspects of the "double-edged sword" role of PARP can be exploited for the experimental therapy of disease. As several classes of PARP inhibitors move towards clinical development, or have already entered the stage of clinical trials, we expect that in the upcoming few years, clinical proof of PARP inhibitors' therapeutic effect will be obtained in human disease. In the current short overview, we summarize the pros and cons and challenges with respect to the clinical use of PARP inhibitors, the expected clinical outcomes and potential risks. It appears that on the cytoprotective aspect of PARP, acute, life-threatening diseases (myocardial infarction, cardiopulmonary bypass in high-risk patients, and other, severe forms of ischemia-reperfusion to other organs including stroke and thoracoabdominal aneurysm repair) may represent some of the prime development indications. In the context of inhibition of DNA repair, combination of PARP inhibitors with certain antitumor agents (for example temozolomide) in patients with tumors with extremely poor prognosis are expected to provide the initial clinical results. Development of PARP inhibitors for additional indications (e.g. chronic use for the therapy of neurodegeneration and neuroinflammation, or diabetic complications) may be more challenging because of the unknown potential long-term side effects of PARP inhibitors.

Original languageEnglish (US)
Pages (from-to)109-118
Number of pages10
JournalPharmacological Research
Volume52
Issue number1 SPEC. ISS.
DOIs
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

Poly(ADP-ribose) Polymerases
temozolomide
DNA Repair
Antineoplastic Agents
Investigational Therapies
Therapeutic Uses
Diabetes Complications
Poly(ADP-ribose) Polymerase Inhibitors
Cardiopulmonary Bypass
Reperfusion
Aneurysm
Cardiovascular Diseases
Ischemia
Stroke
Myocardial Infarction
Clinical Trials
Pharmacology
Wounds and Injuries
Neoplasms
Therapeutics

Keywords

  • Cancer
  • Clinical trials
  • Development
  • Heart
  • Inhibitors
  • Poly(ADP-ribose) polymerase
  • Reperfusion
  • Stroke

ASJC Scopus subject areas

  • Pharmacology

Cite this

Clinical perspectives of PARP inhibitors. / Graziani, Grazia; Szabo, Csaba.

In: Pharmacological Research, Vol. 52, No. 1 SPEC. ISS., 07.2005, p. 109-118.

Research output: Contribution to journalArticle

Graziani, Grazia ; Szabo, Csaba. / Clinical perspectives of PARP inhibitors. In: Pharmacological Research. 2005 ; Vol. 52, No. 1 SPEC. ISS. pp. 109-118.
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