Opportunities and hurdles in the treatment of BRCA1-related breast cancer
Cet article passe en revue les travaux récents sur le rôle de suppresseur de tumeurs joué par la protéine BRCA1 dans les cancers du sein héréditaire et sporadique, puis analyse les perspectives offertes par ces connaissances pour améliorer le traitement des patientes atteintes d'un cancer du sein associé à une mutation de BRCA1
BRCA1 functions as a classical tumor suppressor in breast and ovarian cancer. While the role of BRCA1 in homology-directed repair of DNA double-strand breaks contributes to its tumor suppressive activity, it also renders BRCA1-deficient cells highly sensitive to DNA-damaging agents. Although BRCA1 deficiency is therefore considered to be an attractive therapeutic target, re-activation of BRCA1 by secondary mutations has been shown to cause therapy resistance. In this review, we will assess the role of BRCA1 in both hereditary and sporadic breast cancer and discuss how different functionalities of the BRCA1 protein can contribute to its tumor suppressor function. In addition, we will discuss how this knowledge on BRCA1 function can help to overcome the hurdles encountered in the clinic and improve current treatment strategies for patients with BRCA1-related breast cancer.