• Bulletin du cancer · Oct 2015

    Review

    [From poly(ADP-ribose) discovery to PARP inhibitors in cancer therapy].

    • Valérie Schreiber, Giuditta Illuzzi, Eléa Héberlé, and Françoise Dantzer.
    • Université de Strasbourg, biotechnologie et signalisation cellulaire, UMR7242 CNRS, laboratoire d'excellence Medalis, équipe labellisée ligue 2011, ESBS, 300, boulevard Sébastien-Brant, CS 10413, 67412 Illkirch, France. Electronic address: valerie.schreiber@unistra.fr.
    • Bull Cancer. 2015 Oct 1; 102 (10): 863-73.

    AbstractPoly(ADP-ribosyl)ation is a post-translational modification catalyzed by poly(ADP-ribose) polymerases. PARP-1 is a molecular sensor of DNA breaks, playing a key role in the spatial and temporal organization of their repair, contributing to the maintenance of genome integrity and cell survival. The fact that PARP inhibition impairs efficacy of break repair has been exploited as anticancer strategies to potentiate the cytotoxicity of anticancer drugs and radiotherapy. Numerous clinical trials based on this innovative approach are in progress. PARP inhibition has also proved to be exquisitely efficient to kill tumour cells deficient in double strand break repair by homologous recombination, such as cells mutated for the breast cancer early onset genes BRCA1 or BRCA2, by synthetic lethality. Several phase III clinical trials are in progress for the treatment of breast and ovarian cancers with BRCA mutations and the PARP inhibitor olaparib has just been approved for advanced ovarian cancers with germline BRCA mutation. This review recapitulates the history from the discovery of poly(ADP-ribosyl)ation reaction to the promising therapeutic applications of its inhibition in innovating anticancer strategies. Benefits, hopes and obstacles are discussed.Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

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