Tmod-32. Generation of Glioblastoma Patient Derived Intracranial Xenografts for Preclinical Studies
Year: 2018
Type: conference-abstract
Abstract: Glioblastoma multiforme (GBM) is the most malignant primary brain cancer affecting adults. Therapy options for GBM have remained the same for over a decade with no significant advancements. In vitro cell line models have minimal success for screening potential therapies. Many therapies that were successful in culture have failed in the clinic, likely due to the complex microenvironment in the brain, which has yet to be reproduced in any culture model. Furthermore, high passage number of cultured cells and clonal selection fail to recapitulate the molecular and genomic signatures of GBM. We have been able to successfully establish 37 patient derived xenografts (PDX) intracranially from GBM patient tissue. Tumor derived glial stem cells isolated from patient resected tissue and implanted intracranially into an immunosuppressed mouse strain. Of the 69 patient samples analyzed, we were successful in passaging three or more generations through mice 53.6% of the time. After characterization of the xenografted tumor tissue, two different tumor growth patterns emerged: highly invasive or localized. This phenotype was likely 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. Development of these physiologically relevant mice, will enable therapy screenings in a microenvironment that more closely resembles GBM and may allow development of individualized patient models which can be used for simulating treatment effectors. Once established, intracranial PDX may also be useful for personalizing medicine.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2900440448