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| Home > Articles > Published articles > Sézary syndrome patient-derived models allow drug selection for personalized therapy |
(Hospital del Mar (Barcelona, Catalunya)) (Institut Hospital del Mar d'Investigacions Mèdiques) (Institut Hospital del Mar d'Investigacions Mèdiques) (Institut Hospital del Mar d'Investigacions Mèdiques) (Institut Hospital del Mar d'Investigacions Mèdiques) (Institut Hospital del Mar d'Investigacions Mèdiques) (Hospital del Mar (Barcelona, Catalunya)) (Hospital del Mar (Barcelona, Catalunya)) (Hospital del Mar (Barcelona, Catalunya)) (Hospital del Mar (Barcelona, Catalunya)) (Hospital del Mar (Barcelona, Catalunya)) (Hospital del Mar (Barcelona, Catalunya)) (Hospital del Mar (Barcelona, Catalunya)) (Universidad Complutense de Madrid. Departamento de Microbiología y Parasitología) (Institut Hospital del Mar d'Investigacions Mèdiques) (Institut Hospital del Mar d'Investigacions Mèdiques)
| Date: | 2022 |
| Abstract: | Current therapeutic approaches for Sézary syndrome (SS) do not achieve a significant improvement in long-term survival of patients, and they are mainly focused on reducing blood tumor burden to improve quality of life. Eradication of SS is hindered by its genetic and molecular heterogeneity. Determining effective and personalized treatments for SS is urgently needed. The present work compiles the current methods for SS patient-derived xenograft (PDX) generation and management to provide new perspectives on treatment for patients with SS. Mononuclear cells were recovered by Ficoll gradient separation from fresh peripheral blood of patients with SS (N 5 11). A selected panel of 26 compounds that are inhibitors of the main signaling pathways driving SS pathogenesis, including NF-kB, MAPK, histone deacetylase, mammalian target of rapamycin, or JAK/STAT, was used for in vitro drug sensitivity testing. SS cell viability was evaluated by using the CellTiter-Glo_3D Cell Viability Assay and flow cytometry analysis. We validated one positive hit using SS patient-derived Sézary cells xenotransplanted (PDX) into NOD-SCID-g mice. In vitro data indicated that primary malignant SS cells all display different sensitivities against specific pathway inhibitors. In vivo validation using SS PDX mostly reproduced the responses to the histone deacetylase inhibitor panobinostat that were observed in vitro. Our investigations revealed the possibility of using high-throughput in vitro testing followed by PDX in vivo validation for selective targeting of SS tumor cells in a patient-specific manner. |
| Grants: | Instituto de Salud Carlos III PI19/00013 Instituto de Salud Carlos III PI18/00021 Instituto de Salud Carlos III PI21/0390 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-135 |
| Note: | Fundació Carreras |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Lymphoid Neoplasia |
| Published in: | Blood advances, Vol. 6 Núm. 11 (14 2022) , p. 3410-3421, ISSN 2473-9537 |
