Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies.
Glioblastoma multiforme (GBM) is the most malignant primary brain cancer affecting adults. Therapeutic options for GBM have remained the same for over a decade with no significant improvement. Many therapies that are successful in culture have failed in patients, likely due to the complex microenvironment in the brain, which has yet to be reproduced in any culture model. Furthermore, the high passage number of cultured cells and clonal selection fail to recapitulate the molecular and genomic signatures of GBM. We have established orthotopic patient-derived xenografts (PDX) from 37 GBM patients with human GBM. Of the 69 patient samples analyzed, we were successful in passaging 37 lines three or more generations (53.6%). After phenotypic characterization of the xenografted tumor tissue, two different growth patterns emerged highly invasive or localized. The phenotype was dependent on malignancy and previous treatment of the patient from which the xenograft was derived. Physiologically, mice exhibited symptoms more quickly with each subsequent passage, particularly in the localized tumors. Study of these physiologically relevant human xenografts in mice will enable therapeutic screenings in a microenvironment that more closely resembles GBM and may allow development of individualized patient models which may eventually be used for simulating treatment.
['Kerstetter-Fogle|Amber E|AE|', 'Harris|Peggy L R|PLR|', 'Brady-Kalnay|Susann M|SM|', 'Sloan|Andrew E|AE|']
D000368:Aged D000818:Animals D001921:Brain D001932:Brain Neoplasms D004195:Disease Models, Animal D005260:Female D005909:Glioblastoma D006801:Humans D008297:Male D016688:Mice, Inbred NOD D016513:Mice, SCID D008875:Middle Aged D009368:Neoplasm Transplantation D014407:Tumor Cells, Cultured D059016:Tumor Microenvironment D023041:Xenograft Model Antitumor Assays
intracranial preclinical GBM patient-derived xenograft