dc.contributor.author | Ciscar, M | |
dc.contributor.author | Trinidad, EM | |
dc.contributor.author | Perez-Chacon, G | |
dc.contributor.author | Alsaleem, M | |
dc.contributor.author | Jimenez, M | |
dc.contributor.author | Jimenez-Santos, MJ | |
dc.contributor.author | Perez-Montoyo, H | |
dc.contributor.author | Sanz-Moreno, A | |
dc.contributor.author | Vethencourt, A | |
dc.contributor.author | Toss, M | |
dc.contributor.author | Petit, A | |
dc.contributor.author | Soler-Monso, MT | |
dc.contributor.author | Lopez, V | |
dc.contributor.author | Gomez-Miragaya, J | |
dc.contributor.author | Gomez-Aleza, C | |
dc.contributor.author | Dobrolecki, LE | |
dc.contributor.author | Lewis, MT | |
dc.contributor.author | Bruna, A | |
dc.contributor.author | Mouron, S | |
dc.contributor.author | Quintela-Fandino, M | |
dc.contributor.author | Al-Shahrour, F | |
dc.contributor.author | Martinez-Aranda, A | |
dc.contributor.author | Sierra, A | |
dc.contributor.author | Green, AR | |
dc.contributor.author | Rakha, E | |
dc.contributor.author | Gonzalez-Suarez, E | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-05-30T12:56:07Z | |
dc.date.available | 2023-05-30T12:56:07Z | |
dc.date.issued | 2023-04-11 | |
dc.identifier.citation | EMBO Molecular Medicine, 2023, 15 (4), pp. e16715 - | en_US |
dc.identifier.issn | 1757-4676 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5817 | |
dc.identifier.eissn | 1757-4684 | |
dc.identifier.eissn | 1757-4684 | |
dc.identifier.doi | 10.15252/emmm.202216715 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | e16715 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | WILEY | en_US |
dc.relation.ispartof | EMBO Molecular Medicine | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | ER negative breast cancer | |
dc.subject | RANK-RANKL | |
dc.subject | breast cancer patient-derived xenografts | |
dc.subject | menopause | |
dc.subject | pharmacological RANKL inhibitors | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Denosumab | |
dc.subject | Receptor Activator of Nuclear Factor-kappa B | |
dc.subject | Postmenopause | |
dc.subject | RANK Ligand | |
dc.subject | Signal Transduction | |
dc.title | RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-02-08 | |
dc.date.updated | 2023-05-30T12:54:58Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.15252/emmm.202216715 | en_US |
rioxxterms.licenseref.startdate | 2023-04-11 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36880458 | |
pubs.issue | 4 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Preclinical Modelling of Paediatric Cancer Evolution | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.15252/emmm.202216715 | |
pubs.volume | 15 | |
icr.researchteam | Preclin Paed Cancer Evo | en_US |
dc.contributor.icrauthor | Bruna Cabot, Alejandra | |
icr.provenance | Deposited by Mr Arek Surman on 2023-05-30. Deposit type is initial. No. of files: 1. Files: RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.pdf | |