Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor.
Nat Commun
; 10(1): 5806, 2019 12 20.
Article
em En
| MEDLINE
| ID: mdl-31862972
ABSTRACT
The lack of model systems has limited the preclinical discovery and testing of therapies for Wilms tumor (WT) patients who have poor outcomes. Herein, we establish 45 heterotopic WT patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). Among these 45 total WTPDX, 6 from patients with diffuse anaplastic tumors, 9 from patients who experienced disease relapse, and 13 from patients with bilateral disease are included. Early passage WTPDX show evidence of clonal selection, clonal evolution and enrichment of blastemal gene expression. Favorable histology WTPDX are sensitive, whereas unfavorable histology WTPDX are resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin given singly or in combination. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool to test targeted therapies for WT patient groups with poor outcomes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Tumor de Wilms
/
Resistencia a Medicamentos Antineoplásicos
/
Evolução Clonal
/
Neoplasias Renais
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos