Targeting BRCA Deficiency in Breast Cancer: What are the Clinical Evidences and the Next Perspectives?
1
Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France
2
CRCM-Predictive Oncology laboratory, Institut Paoli-Calmettes, Inserm U1068, CNRS UMR7258, Aix-Marseille Univ, 13009 Marseille, France
*
Author to whom correspondence should be addressed.
Cancers 2018, 10(12), 506; https://doi.org/10.3390/cancers10120506
Received: 8 November 2018 / Revised: 27 November 2018 / Accepted: 9 December 2018 / Published: 11 December 2018
(This article belongs to the Special Issue BRCA Mutations and Cancer)
Breast cancers (BC) associated with germline mutations of BRCA1/2 represent 3–5% of cases. BRCA1/2-associated BC have biological features leading to genomic instability and potential sensitivity to DNA damaging agents, including poly(ADP-ribose) polymerase (PARP) and platinum agents. In this review, we will summarize clinical trials of chemotherapy and PARP inhibitors (PARPi), alone or in combination, at the early or late stage of BRCA1/2-associated BC. We will also present the mechanisms of resistance to PARPi as well as the new therapeutic strategies of association with PARPi. Finally, we will discuss under which conditions the use of DNA damaging agents can be extended to the BRCA1/2-wild type population, the BRCAness concept.
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Keywords:
BRCA; DNA-damaging agents; platinum; poly(ADP)-ribose polymerase
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MDPI and ACS Style
Nicolas, E.; Bertucci, F.; Sabatier, R.; Gonçalves, A. Targeting BRCA Deficiency in Breast Cancer: What are the Clinical Evidences and the Next Perspectives? Cancers 2018, 10, 506.
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