Fiche publication
Date publication
novembre 2017
Journal
Bulletin du cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Dr EBERST Lauriane
Tous les auteurs :
Eberst L, Brahmi M, Cassier PA
Lien Pubmed
Résumé
The transmission of an intact and stable genetic code at each cell division relies on different DNA repair systems. Germline mutations of some of these genes cause cancer predisposition, whereas somatic mutations are frequently found in various cancer types, generating genomic instability. As a consequence, cancer cell becomes more susceptible to additional DNA damage. Pharmacological inhibition of DNA repair pathways exploits this frailty: it triggers more damages than cancer cell can tolerate, finally leading to apoptosis. The success of PARP (poly-ADP-ribose polymerase) inhibitors in BRCA1/2-mutated ovarian cancer shows the clinical relevance of this strategy. Herein, we explain the functioning of different DNA-repair pathways, describe the implicated proteins, and their close relation with cell-cycle checkpoints. We focus on novel therapeutic agents targeting DNA repair, their clinical results, and discuss challenges of combination therapies.
Mots clés
BRCAness, DNA repair, Homologous recombination, Inhibiteurs de PARP, Létalité synthétique, PARP inhibitors, Recombinaison homologue, Réparation de l’ADN, Synthetic lethality
Référence
Bull Cancer. 2017 Nov;104(11):988-998
