Introduction: Current methods to assess potential cancer treatments are cumbersome, and often inaccurate [1]. There is an urgent need to develop new methods to rapidly test interventions for cancer treatment. This need is particularly relevant for glioblastoma multiforme (GBM). In this study, we will use microfluidic platform for delivery of panels of drugs to patient-derived organotypic brain slice cultures with microscale spatiotemporal control and determine drug sensitivity profiles in patient-derived GBM organotypic slice preps. The goals of this study are: i) Characterize temporal changes in GBM slices to understand tissue kinetics ii) Validate cell death readouts in GBM slices iii) Quantify differential drug sensitivity in a series of GBM patient slice cultures.

Methods: We first characterized the temporal changes in GBM slices using GBM samples from 3 adults. GBM tissue obtained through an approved UW IRB protocol in the OR and placed in culture media on ice for immediate transport and sectioning. Temporal changes were quantified by stereologic analysis at 1,3, 5,7, 9, 12 and 15 for cell death, proliferation, and microvascular markers. We used staurosporine on our 3 human GBM slices to develop a standard readout for cell death using PIU and Annexin V signals. Next, we determined differences in dose-response to a panel of 5 GBM drugs with different mechanisms of action in PDSCXs.

Results: Based on the analysis of temporal changes in tissue growth, cell death, proliferation and microvascularization, we observed a heterogeneous profile among 3 GBM patient slices. Dynamic changes in slice geometry, cell death and proliferation occurred within the first few days of patient derived slice cultures. We decided the optimum timing of slice perturbation with selected drugs based on the above parameters.

Conclusions: For a subset of GBM tumors, we are able to establish the ability of the MFSCDx system to detect differential drug responses in PDSCXs.

Patient Care: My research has a potential for personalized treatment of GBM patients through integration with genomics.

Learning Objectives: By the conclusion of this session, I will be able to: 1) Describe the importance of finding new treatments for GBM. Cell lines do not recapitulate microenvironment and with our system we can to preclinical drug testing on patient derived GBM tissues ex vivo, 2) Discuss in small groups and present my research to disseminate scientific knowledge and learn the needs from clinical perspective from clinicians and other scientists, 3) Identify an effective treatment for GBM.

References: [1] Provocative Questions. National Cancer Institute; 2011 [updated 2011; cited]; Available from: http://provocativequestions.nci.nih.gov/rfa.