{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T04:09:41Z","timestamp":1748923781342,"version":"3.41.0"},"posted":{"date-parts":[[2024,11,19]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,2]]},"abstract":"<title>Abstract<\/title>\n        <p>Despite chemotherapy's limitations and toxic effects, it remains the primary treatment for most triple-negative breast cancer (TNBC) patients. While cyclin-dependent kinase 4\/6 inhibitors (CDK4\/6i) combined with endocrine therapy have revolutionized luminal breast cancer treatment, CDK4\/6i alone are largely ineffective in TNBC, even with functional retinoblastoma protein (pRB). The receptor activator of nuclear factor-\u03baB (RANK) pathway has been linked to poor prognosis in TNBC. Previous research connected RANK with resistance to CDK4\/6i in luminal breast cancer, which could be reversed by RANK ligand inhibitors (RANKLi). In this study, RANK knockdown or RANKLi treatment sensitized pRB-proficient TNBC cells to CDK4\/6i, reducing tumor growth and metastasis. Combining CDK4\/6i with RANKLi enhanced cell cycle arrest and elicited an immune response in the tumor microenvironment across BC subtypes. These findings suggest that combining CDK4\/6i and RANKLi is a promising therapeutic approach for pRB-proficient TNBC, with potential immunomodulatory benefits, warranting further investigation.<\/p>","DOI":"10.21203\/rs.3.rs-5377453\/v1","type":"posted-content","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T03:39:53Z","timestamp":1731987593000},"source":"Crossref","is-referenced-by-count":0,"title":["RANK pathway inhibition sensitizes triple-negative breast cancer to CDK4\/6 inhibitors and enhances immune response"],"prefix":"10.21203","author":[{"given":"Sandra","family":"Casimiro","sequence":"first","affiliation":[{"name":"Funda\u00e7\u00e3o GIMM - Gulbenkian Institute for Molecular Medicine"}]},{"given":"In\u00eas","family":"Gomes","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o GIMM - Gulbenkian Institute for Molecular Medicine"}]},{"given":"Maria","family":"Martelo","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o GIMM - Gulbenkian Institute for Molecular Medicine"}]},{"given":"R\u00faben","family":"Vilela","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o GIMM - Gulbenkian Institute for Molecular Medicine"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4696-4705","authenticated-orcid":false,"given":"Sofia","family":"Torres","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade de Lisboa"}]},{"given":"Patr\u00edcia","family":"Corredeira","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o GIMM - Gulbenkian Institute for Molecular Medicine"}]},{"given":"Joana","family":"Miranda","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o GIMM - Gulbenkian Institute for Molecular Medicine"}]},{"given":"Andr\u00e9","family":"Mansinho","sequence":"additional","affiliation":[{"name":"START Lisbon"}]},{"given":"Sofia","family":"Torres","sequence":"additional","affiliation":[{"name":"Unidade Local de Sa\u00fade de Santa Maria"}]},{"given":"Catarina","family":"Abreu","sequence":"additional","affiliation":[{"name":"Unidade Local de Sa\u00fade de Santa Maria"}]},{"given":"Rita","family":"Sousa","sequence":"additional","affiliation":[{"name":"Unidade Local de Sa\u00fade de Santa Maria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-7318","authenticated-orcid":false,"given":"Luis","family":"Costa","sequence":"additional","affiliation":[]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-5377453\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-5377453\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T21:03:44Z","timestamp":1748898224000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-5377453\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-5377453\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1158\/1535-7163.MCT-24-1158","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,11,19]]},"subtype":"preprint"}}