The increasing aging population leads to a rapid rise in cancer incidence and other aging-related disorders, which constitute the main health(care) problems in developed countries world-wide. To accelerate cancer and aging research and contribute to healthy aging, a Mouse Clinic for Cancer and Aging research (MCCA1.0) was established in 2013 by the Netherlands Cancer Institute (NKI) and the European Research Institute for the Biology of Aging (ERIBA). MCCA1.0 aimed to accelerate the development of genetically engineered mouse models (GEMMs) faithfully recapitulating human cancer and aging, and apply these for new therapies against cancer and aging-related diseases. Therefore, three MCCA1.0 facilities were established: 1) a transgenic facility, 2) a mouse cancer clinic and 3) an aging and phenotyping unit.
During 2013-2019, MCCA1.0 established several pillars of success based on innovations, national and international coverage, output and sustainability:
• Novel mouse model generation pipelines for accelerated generation of GEMMs.
• A novel pipeline for generation of somatic breast cancer models.
• A unique biobank for tissues from aged mice.
• A wide coverage with close to 100 (inter)national clients.
• Partner of two European Research Infrastructures, INFRAFRONTIER and EDIReX.
• Completion of 127 new GEMMs and 361 preclinical tumor intervention studies.
• Contribution to 194 peer-reviewed publications, many in high-impact journals.
To maintain and expand its prominent role and to realize further improvements in quality and translation of preclinical research, we now expand towards a Models to Combat Cancer and Aging consortium (MCCA2.0) by including facilities for aging intervention studies, preclinical particle therapy, high-end imaging and pathology, with sites at Erasmus MC, UMC Groningen and Utrecht University.
To make MCCA2.0 live up to its potential and become internationally distinctive, a critical investment is required in new technologies and IT infrastructure for the following reasons:
• Modeling complex diseases such as cancer and aging critically depends on the generation of GEMMs that faithfully mimic human disease. Currently most GEMMs are based on germline modifications. New techniques allow for somatic disease modeling by gene-editing of somatic cells in different organs/tissues.
• Recent breakthroughs in aging research have yielded new intervention strategies to delay many aspects of aging in mice. In wild-type mice, these studies are very time-consuming. The accelerated aging models at MCCA2.0 will speed-up and improve such studies.
• Disease progression and drug interactions in cancer and aging models will be monitored non-invasively with advanced systems for opto-acoustic, molecular and intravital imaging to uncover underlying biological processes and identify novel personalized treatment options.
• MCCA2.0 will provide broad access to recently established unique infrastructures for preclinical proton therapy and single-cell capture and sequencing.
• Reducing animal experimentation is an important national theme. Currently, only a fraction of animal experiments is published. MCCA2.0 will capture all mouse data and provide these under FAIR (Findable, Accessible, Interoperable, Reusable) principles, thus preventing unnecessary repetition and reducing animal numbers.
MCCA2.0 will establish broadly accessible high-end facilities to improve predictivity and reproducibility of preclinical studies and generate data that is findable and accessible to the scientific community. MCCA2.0 will deliver important contributions to early detection methods, new combination therapies and insights in parameters that cause and contribute to aging and aging-related disorders.