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 propose that breast epithelium-specific mono-allelic inactivation of BRCA1 might suffice to cell-autonomously generate RANKL-addicted, denosumab-responsive CSC-like states.  The convergent addiction to a hyperactive RANKL/RANK axis of CSC-like states from genetically diverse breast cancer subtypes might inaugurate a new era of cáncer prevention and treatment based on denosumab as a CSC-targeted agent.

Oncotarget. 2017 May 23;8(21):35019-35032. doi: 10.18632/oncotarget.16558.

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

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Laboratorios Rubió
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Kyowa Kirin