Patient-derived models of brain metastases recapitulate human disseminated disease.
Cell Rep Med
; 3(5): 100623, 2022 05 17.
Article
en En
| MEDLINE
| ID: mdl-35584628
ABSTRACT
Dissemination of cancer cells from primary tumors to the brain occurs in many cancer patients, increasing morbidity and death. There is an unmet medical need to develop translational platforms to evaluate therapeutic responses. Toward this goal, we established a library of 23 patient-derived xenografts (PDXs) of brain metastases (BMs) from eight distinct primary tumors. In vivo tumor formation correlates with patients' poor survival. Mouse subcutaneous xenografts develop spontaneous metastases and intracardiac PDXs increase dissemination to the CNS, both models mimicking the dissemination pattern of the donor patient. We test the FDA-approved drugs buparlisib (pan-PI3K inhibitor) and everolimus (mTOR inhibitor) and show their efficacy in treating our models. Finally, we show by RNA sequencing that human BMs and their matched PDXs have similar transcriptional profiles. Overall, these models of BMs recapitulate the biology of human metastatic disease and can be valuable translational platforms for precision medicine.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Fosfatidilinositol 3-Quinasas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep Med
Año:
2022
Tipo del documento:
Article