Abstract
BackgroundGlioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults, highlighting the need for novel treatment strategies. Patient derived xenografts (PDX) represent a valuable tool to accomplish this task.MethodsPDX were established by implanting GBM tissue subcutaneously. Engraftment success was compared between NMRI Foxn1nu and NOD/SCID as well as between fresh and cryopreserved tissue. Established PDX were analyzed histologically and molecularly. Five PDX were experimentally treated with different drugs to assess their potential for preclinical drug testing.ResultsEstablishment of PDX was attempted for 36 consecutive GBM cases with an overall success rate of 22.2% in NMRI Foxn1nu mice. No difference was observed between fresh or cryopreserved (20–1057 days) tissue in direct comparison (n = 10 cases). Additionally, engraftment was better in NOD/SCID mice (38.8%) directly compared to NMRI Foxn1nu mice (27.7%) (n = 18 cases). Molecular data and histology of the PDX compare well to the primary GBM. The experimental treatment revealed individual differences in the sensitivity towards several clinically relevant drugs.ConclusionsThe use of vitally frozen GBM tissue allows a more convenient workflow without efficiency loss. NOD/SCID mice appear to be better suited for initial engraftment of tumor tissue compared to NMRI Foxn1nu mice.
Highlights
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults, highlighting the need for novel treatment strategies
We present a feasible method for the establishment of GBM Patient derived xenografts (PDX) models from patient tumor material
Individual GBM PDX recommend themselves for this purpose, since tumor material can be propagated for further studies in an in vivo environment, while maintaining intratumoral heterogeneity as well as most genomic aberrations [26]
Summary
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults, highlighting the need for novel treatment strategies. Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults [1, 2]. With a median survival of 14–16 months from diagnosis, the prognosis for GBM patients is very dismal and novel therapeutic strategies are urgently needed to combat this disease [3,4,5,6]. In order to accomplish better personalized therapy strategies, individual models of GBM and sufficient amounts of tumor material for detailed molecular and functional analyses are required. The generation of individual in vitro models of GBM is feasible with success rates of cell culture establishment of approximately 60% [14], in vitro models have
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