Medina Gutiérrez, EsperanzaCéspedes, María VirtudesGallardo, AlbertoRioja Blanco, ElisaPavón Ribas, Miquel ÀngelAsensio Puig, LauraFarré, LourdesAlba Castellón, LorenaUnzueta, UgutzVillaverde, AntonioVázquez, EstherCasanova, IsoldaMangues, Ramon2022-09-122022-09-122022-07-122227-9059https://hdl.handle.net/2445/188909Advanced endometrial cancer (EC) lacks therapy, thus, there is a need for novel treatment targets. CXCR4 overexpression is associated with a poor prognosis in several cancers, whereas its inhibition prevents metastases. We assessed CXCR4 expression in EC in women by using IHC. Orthotopic models were generated with transendometrial implantation of CXCR4-transduced EC cells. After in vitro evaluation of the CXCR4-targeted T22-GFP-H6 nanocarrier, subcutaneous EC models were used to study its uptake in tumor and normal organs. Of the women, 91% overexpressed CXCR4, making them candidates for CXCR4-targeted therapies. Thus, we developed CXCR4(+) EC mouse models to improve metastagenesis compared to current models and to use them to develop novel CXCR4-targeted therapies for unresponsive EC. It showed enhanced dissemination, especially in the lungs and liver, and displayed 100% metastasis penetrance at all clinically relevant sites with anti-hVimentin IHC, improving detection sensitivity. Regarding the CXCR4-targeted nanocarrier, 60% accumulated in the SC tumor; therefore, selectively targeting CXCR4(+) cancer cells, without toxicity in non-tumor organs. Our CXCR4(+) EC models will allow testing of novel CXCR4-targeted drugs and development of nanomedicines derived from T22-GFP-H6 to deliver drugs to CXCR4(+) cells in advanced EC. This novel approach provides a therapeutic option for women with metastatic, high risk or recurrent EC that have a dismal prognosis and lack effective therapies.18 p.application/pdfengcc by (c) Medina Gutiérrez, Esperanza et al., 2022http://creativecommons.org/licenses/by/3.0/es/Càncer d'endometriMetàstasiEndometrial cancerMetastasisinfo:eu-repo/semantics/article2022-08-16info:eu-repo/semantics/openAccess35884987