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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/188909
Novel Endometrial Cancer Models Using Sensitive Metastasis Tracing for CXCR4-Targeted Therapy in Advanced Disease
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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.
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MEDINA GUTIÉRREZ, Esperanza, CÉSPEDES, María virtudes, GALLARDO, Alberto, RIOJA BLANCO, Elisa, PAVÓN RIBAS, Miquel àngel, ASENSIO PUIG, Laura, FARRÉ, Lourdes, ALBA CASTELLÓN, Lorena, UNZUETA, Ugutz, VILLAVERDE, Antonio, VÁZQUEZ, Esther, CASANOVA, Isolda, MANGUES, Ramon. Novel Endometrial Cancer Models Using Sensitive Metastasis Tracing for CXCR4-Targeted Therapy in Advanced Disease. _Biomedicines_. 2022. Vol. 10, núm. 7, pàgs. 1680. [consulta: 23 de gener de 2026]. ISSN: 2227-9059. [Disponible a: https://hdl.handle.net/2445/188909]