[PARP inhibitors and breast cancer: update and perspectives].

Abstract

Poly(ADP-ribose) polymerase (PARP) family has become a promising therapeutic target in various malignancies including breast cancer. When homologous recombination repair is deficient, as it is observed in BRCA1/2-mutated tumor models, inhibition of PARP was shown to induce massive and selective tumor cell death (the so-called "synthetic lethality"). In breast cancer, PARP inhibitors have been developed as single-agent in BRCA1/2-mutated tumors or in combination with chemotherapy. Recently, a randomized phase III clinical trial failed to demonstrate any survival improvement by combining the iPARP iniparib to chemotherapy in triple-negative metastatic breast cancer patients. This emphasizes the need for future development of this class of compounds to resolve critical issues such as optimal schedule of administration and association to other anticancer treatments, as well as identification of pertinent biomarkers predictive for efficacy.

• Authors: Anthony Gonçalves
• Journal: Bulletin du cancer (Bull Cancer) Vol. 99 Issue 4 Pg. 441-51 (Apr 01 2012) ISSN: 1769-6917 [Electronic] France
• Vernacular Title: Inhibiteurs de la poly(ADP-ribose) polymerase et cancer du sein : bilan et perspectives.
• PMID: 22450359 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Benzamides
• Drugs, Investigational
• Enzyme Inhibitors
• Phthalazines
• Piperazines
• Poly(ADP-ribose) Polymerase Inhibitors
• iniparib
• Poly(ADP-ribose) Polymerases
• olaparib

Topics

• Antineoplastic Agents (therapeutic use)
• Benzamides (therapeutic use)
• Breast Neoplasms (drug therapy, enzymology, genetics)
• Cell Death (genetics)
• DNA Repair (physiology)
• Drug Synergism
• Drugs, Investigational (therapeutic use)
• Enzyme Inhibitors (therapeutic use)
• Female
• Genes, BRCA1
• Genes, BRCA2
• Humans
• Mutation
• Phthalazines (therapeutic use)
• Piperazines (therapeutic use)
• Poly(ADP-ribose) Polymerase Inhibitors
• Poly(ADP-ribose) Polymerases (metabolism)
• Recombinational DNA Repair