Efficacy of chemical and biological compounds is assessed on panels of patient-derived glioma cells. Tumor cells are plated onto coated 96-wells plates in optimal culture medium* and are exposed to different concentrations and combinations of drugs. At multiple time points after treatment, viability is determined using a luminescent or fluorescent chemical viability assay* as well as by assessment of confluence by a kinetic live-cell imaging system. Together, these assays provide a reliable measure of cell viability, allowing IC50 calculation. Agents can be tested alone or in combination with each other. For combination studies, Chou-Talalay synergy quantification is applied. Valuable information can be obtained on potentially synergistic interactions between drugs.
*based on stringent analysis and comparison of multiple dissociation protocols, matrix coatings, culture medium formulas, and commercially available viability assays
For most agents large inter-tumoral variation is seen, which generally translates to responders, non-responders and intermediate responders. For example, the graph depicts variation in response to Temozolomide treatment. Whereas GS102 shows a dose-dependent decrease in viability upon TMZ treatment, GS265 remains completely refractory to this agent
GLIOscreen also offers the opportunity to identify compounds that increase the response rate to standard therapy. The graph below, for example, depicts an example of effective combination treatment. The percentage of glioma cell cultures (of 34 tested samples) that respond* to standard treatment of Temozolomide and radiotherapy increases by combining these therapies with each other or with an HDAC inhibitor and reaches almost 90% when applying the triple treatment of TMZ+RT+HDACi.
*Response is defined as more than 75% decrease in viability over 5 days.