Sistema de Salut de Catalunya
Institut Català de la Salut
[Sengal AT] Endometrial Cancer Laboratory, School of Biomedical Sciences, Faculty of Health, the Queensland University of Technology located at the Translational Research Institute (TRI), Kent St Woolloongabba, Brisbane, Australia. [Bonazzi V] Endometrial Cancer Laboratory, School of Biomedical Sciences, Faculty of Health, the Queensland University of Technology located at the Translational Research Institute (TRI), Kent St Woolloongabba, Brisbane, Australia. Frazer Institute, The University of Queensland, Brisbane, Australia. [Smith D, Lourie R, Rogers R] Mater Pathology, Mater Health, Brisbane, Australia. [Moiola CP, Colas E, Gil-Moreno A] Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBERONC, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2024-01-08T10:43:16Z
2024-01-08T10:43:16Z
2023-12-08
Endometrial cancer; Immunohistochemistry; Predictive markers
Càncer d'endometri; Immunohistoquímica; Marcadors predictius
Cáncer de endometrio; Inmunohistoquímica; Marcadores predictivos
Endometrial cancer (EC) patients with metastatic/recurrent disease have limited treatment options and poor survival outcomes. Recently, we discovered the FGFR2c splice isoform is associated with poor prognosis in EC patients. Here we report the establishment of 16 EC patient-derived xenografts (PDX)-derived organoids (PDXOs) with or without FGFR2c expression. In vitro treatment of 5 EC PDXOs with BGJ398 showed significant cell death in 3 models with FGFR2c expression. PDXs with high/moderate FGFR2c expression showed significant tumour growth inhibition (TGI) following 21-day treatment with FGFR inhibitors (BGJ398 or pemigatinib) and significantly prolonged survival in 4/5 models. Pemigatinib + cisplatin combination therapy (n = 5) resulted in significant TGI and prolonged survival in one of two p53abn PDXs. All five models treated with cisplatin alone showed de novo resistance and no survival benefit. Seven-day treatment with BGJ398 revealed a significant reduction in angiogenesis and CD206 + M2 macrophages. These data collectively support the evaluation of FGFR inhibitors in a clinical trial.
Article
Versió publicada
Anglès
Teixits - Remodelació; Endometri - Càncer - Tractament; Factor de creixement epidèrmic - Inhibidors; DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Endometrial Neoplasms; ANATOMY::Tissues::Organoids; CHEMICALS AND DRUGS::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gastrointestinal Hormones::Epidermal Growth Factor; Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias endometriales; ANATOMÍA::tejidos::organoides; COMPUESTOS QUÍMICOS Y DROGAS::hormonas, sustitutos de hormonas y antagonistas de hormonas::hormonas::hormonas gastrointestinales::factor de crecimiento epidérmico; Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores
Nature Portfolio
npj Precision Oncology;7
https://doi.org/10.1038/s41698-023-00478-6
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - VHIR [1655]
