RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.

Autor: Ciscar M; Molecular Oncology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain., Trinidad EM; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain., Perez-Chacon G; Molecular Oncology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Alsaleem M; Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Jimenez M; Molecular Oncology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Jimenez-Santos MJ; Bioinformatics Unit, Structural Biology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Perez-Montoyo H; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain., Sanz-Moreno A; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain., Vethencourt A; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.; Medical Oncology, Breast Unit, Catalan Institute of Oncology (ICO), University Hospital of Bellvitge, Barcelona, Spain., Toss M; Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Petit A; Pathology Department, University Hospital of Bellvitge, IDIBELL, Barcelona, Spain., Soler-Monso MT; Pathology Department, University Hospital of Bellvitge, IDIBELL, Barcelona, Spain., Lopez V; Molecular Oncology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Gomez-Miragaya J; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain., Gomez-Aleza C; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain., Dobrolecki LE; Molecular and Cellular Biology and Radiology, The Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, USA., Lewis MT; Molecular and Cellular Biology and Radiology, The Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, USA., Bruna A; Cancer Research UK Cambridge Centre, Cambridge, UK., Mouron S; Breast Cancer Clinical Research Unit, Clinical Research Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Quintela-Fandino M; Breast Cancer Clinical Research Unit, Clinical Research Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Al-Shahrour F; Bioinformatics Unit, Structural Biology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Martinez-Aranda A; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.; Medical Oncology, Breast Unit, Catalan Institute of Oncology (ICO), University Hospital of Bellvitge, Barcelona, Spain., Sierra A; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain., Green AR; Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Rakha E; Nottingham Breast Cancer Research Centre, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham, UK., Gonzalez-Suarez E; Molecular Oncology, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.; Oncobell, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
Jazyk: angličtina
Zdroj: EMBO molecular medicine [EMBO Mol Med] 2023 Apr 11; Vol. 15 (4), pp. e16715. Date of Electronic Publication: 2023 Mar 07.
DOI: 10.15252/emmm.202216715
Abstrakt: Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein expression in more than 2,000 breast tumors (777 estrogen receptor-negative, ER - ) from four independent cohorts. RANK protein expression was more frequent in ER - tumors, where it associated with poor outcome and poor response to chemotherapy. In ER - breast cancer patient-derived orthoxenografts (PDXs), RANKL inhibition reduced tumor cell proliferation and stemness, regulated tumor immunity and metabolism, and improved response to chemotherapy. Intriguingly, tumor RANK protein expression associated with poor prognosis in postmenopausal breast cancer patients, activation of NFKB signaling, and modulation of immune and metabolic pathways, suggesting that RANK signaling increases after menopause. Our results demonstrate that RANK protein expression is an independent biomarker of poor prognosis in postmenopausal and ER - breast cancer patients and support the therapeutic benefit of RANK pathway inhibitors, such as denosumab, in breast cancer patients with RANK + ER - tumors after menopause.
(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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