Ciência e terapia do câncer

A Comprehensive Approach to Patient-individual Glioblastoma Multiforme Model Establishment

Abstract

Christina Susanne Mullins, Björn Schneider, Anne Lehmann, Florian Stockhammer, Sascha Mann, Carl-Friedrich Classen and Michael Linnebacher

Patient-individual tumor models for Glioblastoma Multiforme (GBM) are important not only for basic and translational research but also for the development and improvement of optimal and individualized treatment strategies. The model that has gained widest acceptance is the primary cell culture model. The laborious and time consuming process is rewarded with a relative high initial success rate (about 60%). We here describe and evaluate an extended biobanking methodology to simplify sample collection and model establishment. GBM resection specimen were collected ad hoc, partially prepared fresh for modeling, snap frozen for molecular testing and frozen down vitally.

The established models were subject to subsequent detailed characterization in direct comparison to the patients´ tumors. Generally, molecular characteristics such as mutations, gene amplifications and epigenetic alterations were maintained in the models. Immortality, neuronal origin and stem cell characteristics of the cell lines could be demonstrated. Extensive drug sensitivity screens were performed. These well-defined patient-individual models are ideal for establishment of individualized therapy approaches and enable testing of immunological strategies.

Our extended biobanking procedure facilitates collection, long-time storage and propagation (modeling) of clinical GBM specimens (potentially also from distant centers) for basic research, (pre-) clinical studying of novel therapies and individual response prediction.