Project Details
Projekt
CP1: Translational platform for PDAC model generation and drug response characterization
Applicants
Professor Dr. Matthias Dobbelstein; Professorin Dr. Elisabeth Heßmann; Privatdozentin Dr. Silke Kaulfuß; Professor Dr. Günter Schneider; Professor Dr. Philipp Ströbel; Professor Dr. Bernd Wollnik
Subject Area
Gastroenterology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426671079
The prime goal of the CRU 5002 is to decipher the mechanistic, functional and therapeutic consequences of subtype-specific and subtype-overlapping genome dynamic alterations in pancreatic cancer (PDAC). To achieve this aim, the consortium relies on molecularly characterized patient-derived PDAC models suitable for comprehensive applications ranging from detailed mechanistic studies to pre-clinical drug testing. To this end, Core Project 1 (CP1) has established a translational PDAC model platform comprising Patient-Derived-Xenograft (PDX) models, PDX-derived primary PDAC cells (CDX) and patient-derived-organoid (PDOs) models for joint utilization within and beyond the CRU 5002. PDAC models have been generated from 106 clinically comprehensively documented PDAC patients of the Molecular Pancreas Program (MolPAC) of the University Medical Center Göttingen (UMG) with resectable disease and underwent detailed molecular characterization at the genomic and expression (transcriptome and immunohistochemistry) level. Since the CRU 5002 now envisions to study the impact of genome dynamics in all disease stages, we will extend and adjust our pipelines for the generation of preclinical models to specimens from (locally) advanced MolPAC PDAC patients. Further, CP1 will function as the interface of the CRU5002 and the Molecular Tumor Board (MTB) of the UMG and will benefit from the MTB pipeline as a temporally distinct second source of PDAC samples and models. Finally, CP1 will offer an in vitro PDAC model platform for basal functional characterization of PDO and CDX models and standardized and quality-controlled assessment of drug (combination) responses. Together, we envision CP1 to substantially support the CRU5002 in dissecting the biological significance and the therapeutic consequences of genome dynamics in PDAC and to speed up the translational potential of CRU5002 findings.
DFG Programme
Clinical Research Units
