DKTK - Research Program "Molecular Diagnostics, Early Detection and Biomarker Development (MDEB)"

For the DKTK Organoid Platform, we will implement advanced single cell technologies for characterizing a selected set of organoids from the MetPredict and NeoMatch cohorts. For MetPredict, DKTK partners aim to establish between 4 and 6 PDOs from each patient to comprise combined patient- and lesion-individualized in vitro models. Patients with a diffuse relapse pattern of hepatic metastases will be the primary targets for in depth single cell characterization to provide information of the phenotypic heterogeneity within a patient. For NeoMatch, we will perform scRNAseq of matched pairs of treatment-naïve and treatment-exposed PDOs to determine unique and shared dynamics of EMT heterogeneity and plasticity. This comprehensive transcriptional characterization of matched PDOs will then be complemented with CyTOF from treatment-exposed PDOs and by image mass cytometry (IMC) of corresponding tissues from surgical resections after neoadjuvant chemotherapy.  To this end, we will develop - similarly to the establishment of our CRC panel - a PDAC CyTOF panel to capture the EMT continuum under therapy in vitro and in vivo. Overall, by combining these unique clinical cohorts with organoid technology and advanced single-cell profiling we will be able to provide in-depth molecular insights on cell states, molecular traits of metastases and phenotypic response to therapy.

Timeline:

• 2023 - 2025