BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells.

Denosumab, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), might be a novel preventative therapy for BRCA1-mutation carriers at high risk of developing breast cancer. They tested the alternative but not mutually exclusive hypothesis that BRCA1 deficiency might cell-autonomously activate RANKL expression to generate cellular states with cancer stem cell (CSC)-like properties. Using isogenic pairs of normal-like human breast epithelial cells in  which the inactivation of a single BRCA1 allele results in genomic instability,we assessed the impact of BRCA1 haploinsufficiency on the expression status of RANK and RANKL.

Oncotarget. 2017 Mar 25. doi: 10.18632/oncotarget.16558.

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Cuyàs E, Corominas-Faja B, Muñoz-San Martín M, Martin-Castillo B, Lupu R, Brunet J, Bosch-Barrera J, Menendez JA.

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Laboratorios Rubió
Grupo Italfármaco
Gedeon Richter
Kyowa Kirin