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The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy

Lookup NU author(s): Professor Nicola CurtinORCiD

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Abstract

The modulation of DNA repair pathways for therapeutic benefit in cancer has now become a reality with the development of poly (ADP-ribose) polymerase inhibitors (PARPi). PARP is involved in single-strand DNA breaks, which in the presence of defective homologous recombination repair lead to double-strand DNA breaks, the most lethal form of DNA damage. These agents therefore may be the drugs of choice for BRCA mutant breast and ovarian cancers. PARPi result in synergistic antitumor effects when combined with cisplatin, temozolomide, topoisomerase inhibitors and ionizing radiation. The indications for PARPi lie beyond BRCA mutations and may include genomic and functional defects in DNA repair and damage response pathways. Several PARPi are in the clinical development phase at this time and, given the recent failure of a phase III clinical trial of iniparib in triple-negative breast cancer, the identification of structural and functional differences between these inhibitors becomes critical. Acquired resistance to PARPi is being noted and represents an important limitation in this field. A concise review of the literature in this field is presented.

Publication metadata

Author(s): Javle M, Curtin NJ

Publication type: Article

Publication status: Published

Journal: Therapeutic Advances in Medical Oncology

Year: 2011

Volume: 3

Issue: 6

Pages: 257-267

Print publication date: 15/08/2011

ISSN (print): 1758-8340

ISSN (electronic): 1758-8359

Publisher: Sage Publications Ltd.

URL: http://dx.doi.org/10.1177/1758834011417039

DOI: 10.1177/1758834011417039

PubMed id: 22084640

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