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Ex Vivo Drug Response Evaluation for Next Generation Care of Brain Metastases

Pharmacoscopy refers to an ex vivo real-time drug sensitivity profiling platform that has been shown to be of value in the treatment of leukemia (Snijder et al. 2017) (Kornauth et al. 2022) and may help to identify novel treatment opportunities for brain tumors as well (Lee et al. 2022). The rationale for pharmacoscopy-based drug sensitivity testing on real-time patient biopsies or surgery material is multiple: measuring drug response and sensitivity directly in real-time patient material, overcomes the problem of limited molecular biomarkers for established targeted therapeutic options and can identify effective drugs even for non-targeted therapies such as chemotherapy. It can also identify hitherto unknown specific vulnerabilities of cancer cells. Furthermore, testing directly on patient material overcomes the limitations of patient-derived cell cultures, organoids, and patient xenografts, as their prolonged culture times risk cellular adaptations and clonal selection that alter drug sensitivity. Pharmacoscopy maintains the tumor cell composition, including bystander cells or tumor microenvironment, and limits cell culture to max 48 hours. Furthermore, pharmacoscopy measures drug responses on a single-cell and on a high-content level, uniquely allowing to measure the drug sensitivity of tumor cells, and allowing to compare it to the drug cytotoxicity on healthy cells from the same patient. This relative readout has previously been shown to be essential for the correct prediction of a clinical response in haematological malignancies (Snijder et al. 2017) (Kornauth et al. 2022). The aim of this study is to generate preliminary data regarding superiority of the personalized pharmacoscopy-guided approach compared to a standard non-pharmacoscopy-guided approach, in patients with brain metastases with an indication for surgery, and limited therapeutic systemic options according to the treating physician.