Journal
CELL REPORTS MEDICINE
Volume 3, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.xcrm.2022.100623
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Funding
- Fundacao para a Ciencia e a Tecnologia (FCT) [SFRH/BD/140299/2018, PD/BD/128288/2017, PTDC/MED-ONC/32222/2017]
- Fundacao Millennium bcp
- FCT/Ministerio da Ciencia, Tecnologia e Ensino Superior (MCTES) [UID/BIM/50005/2019]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/140299/2018, PD/BD/128288/2017, PTDC/MED-ONC/32222/2017] Funding Source: FCT
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This study established a library of patient-derived xenografts of brain metastases and demonstrated their similarity to human metastatic disease. The efficacy of two drugs was tested, and RNA sequencing revealed similar transcriptional profiles between human brain metastases and the xenografts.
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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