Integrative analyses of drug responses in tumor organoids of brain metastases
The occurrence of breast cancer brain metastases (BCBM) is one of the most dismal prognostic factors for patient survival. However, knowledge about the specific sensitivity of brain metastatic breast cancer cells to drugs is still limited. Such insights are crucial for optimizing drug selection and tailoring therapies for individual patients.
In this project, we conducted personalized high-throughput drug screenings including > 250 drugs on patient-derived BCBM cell lines using the Heidelberg drug screening platform experimental neurosurgery (HeiDePEx) platform. The platform integrates the biobanking of diverse biological specimens from brain tumor patients with ex vivo models, multi-omics, spatial analyses, and functional drug screenings. Selected effective drugs are further tested in a highly standardized tumor organoid model, which particularly preserves intra-tumoral heterogeneity. The findings were validated and further explored in reference to patient-individual multi-omics data obtained within the CATCH study (metastatic breast cancer precision oncology program), integrating drug screening results, clinical, and molecular data. The screening results revealed heterogeneity in drug responses for each cell line. Notably, genomic analysis revealed the cell lines maintained key molecular characteristics of tumor tissues, and their drug response data aligned with the CATCH data. Together, this underscores the necessity for personalized treatment strategies and emphasizes the significance of precision medicine for BCBM patients. Our findings highlight the value of this integrative approach in understanding drug mechanisms and optimizing treatments for individual BCBM patients.
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Live/dead image of breast cancer brain metastases (BCBM) organoid. The organoid was generated from freshly resected BCBM tissues. Live/dead staining was performed after 7 days of cultivation. Green fluorescence indicates the live cells and red fluorescence indicates the dead cells.
Scale bar: 200 µm.