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| Home > Articles > Published articles > Novel Endometrial Cancer Models Using Sensitive Metastasis Tracing for CXCR4-Targeted Therapy in Advanced Disease |
| Home > Articles > Published articles > Novel Endometrial Cancer Models Using Sensitive Metastasis Tracing for CXCR4-Targeted Therapy in Advanced Disease |
(Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut d'Investigació Biomèdica de Bellvitge) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
| Date: | 2022 |
| Abstract: | Advanced 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. |
| Grants: | Instituto de Salud Carlos III PI21/00159 Instituto de Salud Carlos III PI18/00650 Instituto de Salud Carlos III PI20/00400 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-865 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-229 Instituto de Salud Carlos III CP19/00028 Instituto de Salud Carlos III CPII20/00007 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Published in: | Biomedicines, Vol. 10 Núm. 7 (july 2022) , p. 1680, ISSN 2227-9059 |
