Development of PARP inhibitors in oncology.

Abstract:

:Poly (ADP-ribose) polymerase (PARP) plays a key role in DNA repair mechanisms by detecting and initiating repair after DNA strand breaks. Inhibition of PARP in DNA repair-defective tumors (like those with BRCA1 or BRCA2 mutations) can lead to gross genomic instability and cell death. Likewise, combining PARP inhibition with cytotoxic agents such as chemotherapy or radiation therapy is synergistic in many preclinical models. Several drugs designed to inhibit PARP are currently in clinical development, many following a development path different from that of typical anticancer agents. In this review we will focus on the early clinical data from PARP inhibitors that are entering clinical trials, the potential tumors they might target, their combination with other drugs and the different biomarkers that are being explored. Concepts such as 'BRCAness', synthetic lethality, Phase 0 trials and pharmacodynamic markers will be discussed in the context of the development of PARP inhibitors.

authors

Rodon J,Iniesta MD,Papadopoulos K

doi

10.1517/13543780802525324

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

31-43

issue

1

eissn

1354-3784

issn

1744-7658

journal_volume

18

pub_type

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