1. Animal Models in Cancer Research Ulli Wagner. November 4, 2010

2. In the News

3. Animal Models – different Species Drosophila C. elegans Mouse Rat Other Laboratory Animals Rabbit Zebrafish Hamster Cancer in Other Animals Dog Cat Horse Pig Goat

4. Types of Animal Models Inbred Mice and Rats Brother & sister matings for > 20 generations Inbred strains are considered isogenic (genetically identical) Different strains harbor different characteristics Tumor Frequency Grid

5. Types of Animal Models Carcinogen-induced models Exposure to chemicals like DMBA (oral cancer in hamster models, mammary gland cancer in mice) Exposure to radiation (UV light -> skin cancer) Hormones, growth factors, nutritional factors, viruses …

6. Types of Animal Models Transplantation models Allograft transplantation model Immuno-competent recipient Host and graft have same genetic background Xenograft transplantation models Immuno-incompetent recipient Host = mouse, graft = human Fresh tissue or immortalized cell lines Transplantation location Orthotopic Subcutaneous etc

7. Types of Animal Models Genetically modified N-ethyl-N-nitrosourea (ENU) mutagenesis Random mutagenesis Transgenic animals Carrying one or more foreign genes Depending on the promoter transgene gets turned on time- and/or tissue- specific Targeted modifications Knock- out mice (p53 knockouts – Li-Fraumeni Syndrome) Conditional knockout mice e.g. using the Cre-lox system Tetracycline-controlled transcriptional activation Level of complexity to modeling

8. Types of Animal Models Spontaneous Mutations Laboratory animal (genetic screening) Companion animals – share the same environment Cats Dogs

9. Research uses of Animal Models Increase our knowledge of the biology of normal and malfunctioning cells Improve the efficacy and safety of chemical and non-chemical interventions Identify preventive measures Raise awareness of susceptibility and risks Aid in developing imaging technologies

10. caMOD The Cancer Models Database Submission—Data extracted from literature by curators or submitted by scientists. Search– Customizes searches or predefined searches. System Function Administration— User management and review of models. caMOD is a web-based resource that provides information about animal models for human cancer to the public research community http://cancermodels.nci.nih.gov

11. History January 2000 Prototype is presented during the Mouse Models of Human Cancers (MMHCC) Steering Committee Meeting MMHCC adopts the Cancer Models Database (caMOD) as one of their initiatives July 2000 NCICB assumes responsibility for caMOD Spring 2001 caMOD 1.0 released (2-tier application) December 2005 caMOD 2.0 released (n-tier application, based on caBIG compliance guidelines) July 2007 caMOD 2.1 achieves Silver compatibility December 2008 caMOD 2.5 released (grid service) September 2009 caMOD 2.5 achieves Silver compatibility June 2010 caMOD 2.6.1 released October 2010 caMOD 2.6.2 released

12. Status 6,037 models 5,946 Mouse entries 42 Dog entries 13 Rat entries 10 Rabbit entries 9 Zebrafish entries 6 Hamster entries 5 Horse entries 4 Cat entries 1 Goat entry 1 Sheep entry

13. The Backbone Model Characteristics = Overview Genetic Description, Carcinogenic Interventions and Transplantation describe in more detail how the model was generated. Other parts describe the results of experiments performed or observations made on this particular strain.

14. Modularity = Endurance and Flexibility Most parts contain multiple pages Multiple entries per category are possible

15. What makes caMOD unique? Variety of species Inclusion of transplantation models Inclusion of therapy data Efforts to provide cross-species comparisons of therapeutic results caMOD has been designed, architected and constructed to facilitate interoperability with other systems, following caBIG guidelines. Silver-compatible (Data elements in caDSR, available for reuse) Grid-enabled Use of controlled vocabularies (EVS)

16. Animal Models - Summary Animal models recapitulate many aspects of the genesis progression clinical course of human cancers They are valuable resources in a variety of basic, translational, clinical, and epidemiological investigations.

17. More Information eMICE Website: http://emice.nci.nih.gov Jax (including MTB) http://www.informatics.jax.orghttp:// Rat Genome Database (RGD) http://rgd.mcw.edu/ The Zebrafish Model Organism Database (ZFIN) http://zfin.org caMOD http://cancermodels.nci.nih.gov NCI’s Comparative Oncology Program (Dogs) https://ccrod.cancer.gov

18. Acknowledgements NCI Juli Klemm, Ph.D Cheryl Marks, Ph.D. MMHCC & all contributors Development team Maki Duncan (5AM Solutions) Sima Pandya (SAIC) Curator Maureen Colbert (SAIC)