医学
疾病
转化医学
癌症
癌症研究
PI3K/AKT/mTOR通路
转化研究
依维莫司
心内注射
肿瘤科
生物信息学
内科学
病理
生物
信号转导
生物化学
作者
Cláudia Faria,Rita Cascão,Carlos Custódia,Eunice Paisana,Tânia Carvalho,Pedro Pereira,Rafael Roque,José Pimentel,José Miguéns,Isidro Cortes-Ciriano,João T. Barata
标识
DOI:10.1016/j.xcrm.2022.100623
摘要
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.
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