Proof-of-concept platform for translational cancer research
Preclinical models
Both the pathogenesis and the therapy of tumors and the development of resistance are influenced by multiple factors. These include organ-specific differences, variable oncogenic mutations, the tumor micro- and macroenvironment and interaction with the immune system. The lack of or limited consideration of these dependencies in disease models limits the transferability of research results from model systems (e.g. cell lines) to clinical reality. The availability and quality of preclinical models is crucial for all aspects of translation, from the discovery of new therapeutic target structures, their validation and preclinical testing to the modeling of resistance mechanisms.
The potential of the BZKF lighthouse "preclinical models" is to create basic structures that facilitate the provision, application and further development of high-quality preclinical models for translational oncology in the BZKF.
One of the main goals of the lighthouse is to establish organ-specific organoid (so-called 3D models) units. These central units will enable researchers in the BZKF network to develop and test preclinical models at an unprecedented level of detail. The resulting findings will help to narrow the gap between basic (preclinical) science and early clinical application.
Successful basic research working groups in the field of tumor research and (early) clinical study units for tumor therapy studies have been established at all BZKF sites. However, there is currently a gap between these structures. In particular, there is a lack of uncomplicated and unbureaucratic availability of preclinical models in the context of "forward translation" in order to test the basic scientific findings for their fundamental clinical applicability.
This will
- narrow the gap between (preclinical) basic science and early clinical application,
- establish a structured basis for the exchange of preclinical models in the BZKF and
- shorten the time needed to carry out proof-of-concept studies.
Organoids and relevant information on common tumor entities are collected in the organ-specific organoid unit. This includes molecular and clinical data, which is regularly updated.
The Preclinical Animal Experimentation Unit is to become an administrative and scientific contact point for the conception of animal experimentation applications. To this end, the unit supports the scientists and provides informative templates in coordination with the approval authorities.
The Target Validation Unit establishes auxin mouse models as a new preclinical tool.
This model leads to the degradation of oncogenic target proteins in tumors that are not yet therapeutically addressable. It thus serves to identify and evaluate potential target structures for PROTAC-based therapy.
SOPs for the use of this innovative preclinical target validation system will be made available to all BZKF sites.
Organ-specific organoid unit
- In addition to the creation of a database, the collection and
and establishment of common organoid tumor entities will be promoted.
- Ethics votes, data protection and governance concepts are being worked on together with the BZKF's data protection lawyer.
- Collection of sequencing data of tumor-specific driver mutations.
- Provision of patient-relevant data through collaboration with the local tumor documentation centers.
Preclinical animal testing unit
By harmonizing text modules, the time frame for applying for animal testing projects should become easier to calculate.
This is to be achieved by establishing
- an information channel between the sites to create a clear and uniform description of the performance of interventions on animals in the form of SOPs.
- the filing of approved annexes to animal experimentation projects such as score sheets.
- Optimization of the exchange of information between the research institutions (including
scientists, animal welfare officers) and regulatory authorities.
- Establishment of a proof-of-concept platform for a joint organoid database and a database for oncologically relevant preclinical animal models
- Objective of the organoid database: to provide researchers with material and information on organoids of various tumor entities for their preclinical research
- Objective of the database for preclinical animal models: to provide researchers with detailed information on site-specific animal models and to provide an information tool to support the preparation of animal experiment applications
- To make the auxin mouse model available to the entire network as a preclinical target validation system for PROTAC development.
