Through a number of new initiatives the CCR has created an essential infrastructure to improve the translational research process. To compliment these efforts the CCR launched the Comparative Oncology ( mission has been to provide an integrated mechanism by which naturally occurring cancer models can be used to generate new information about cancer, translate biological concepts towards clinical application and bring novel therapeutic options to the management of human cancers. The initial goals of the CCR - Comparative Oncology Program: 1. Develop essential reagent kit for the study of comparative models in translational and biology-based research. Specific reagents/resources include: COTC Pharmacodynamic Core: This multidisciplinary effort operates as a laboratory with """"""""virtual walls"""""""" consisting of services provided by investigators who have competed for the opportunity to contribute to the assay/procedure service catalog of the Core. The COTC PD CORE is meant to facilitate early discussions with COTC trial sponsors (pharmaceutical companies) by providing the infrastructure for rapid implementation of preclinical studies needed to initiate a COTC study and then seamlessly support the clinical pharmacodynamic and biological endpoints of COTC trials. In FY 2010 the COTC PD Core was used to support 3 different COTC trials. A manuscript detailing the creation of the COTC PD Core infrastructure was published in The Veterinary Journal. Canine oligonucleotide microarray: Optimized techniques and normal tissue expression standards for both a first generation and more recently a second generation canine oligonucleotide microarray have been completed and initiated. This microarray is currently available through Affymetrix. In FY 2010: 1) Manuscript comparing the gene signatures or canine and human osteosarcoma was published in BMC Genomics. This work was in collaboration with Dr. Paul Meltzer's group the Molecular Genetics Section,, 2) The project to characterize the gene signatures of 10 normal canine tissues in collaboration with Dr. Javed Khan's Oncogenomics Section, and establish a database available for public search was completed. The manuscript detailing this approach is submitted for publication. Serum proteomics (SELDI-TOFF): Conditions for canine serum proteomic analysis have been optimized in collaboration with Timothy Veenstra (Biological Proteomics Program). Validated antibody data base: A database of validated antibodies for use in canine tissues is being developed within the Comparative Oncology Program in collaboration with commercial antibody vendors and Dr. David Goldsmith and is available to the public ( (Center for Cancer Research). Canine Comparative Oncology Genomics Consortium (CCOGC): Using its neutral position, the Comparative Oncology Program has brought together a broad representation of parties (academic, industry, government) focused on the genetics and biology of cancer in dogs. The shared interests of the CCOGC will result in further genomics reagent/resource development and collaborative efforts that will characterize canine cancers as molecular models of human disease. In 2007, the CCOGC launched the Pfizer-Canine Comparative Oncology and Genomics Consortium Biospecimen Repository. The Repository is currently working toward its goal of collecting 3000 patient samples in 3 years. Canine Cancer Biospecimen Repository: A biospecimen respository of frozen, and formalin fixed tissues from dogs with cancer has been established through a contract with Fisher Bioservices. The collection of samples to populate this bank will occur through clinical trials conducted by the Comparative Oncology Trials Consortium (COTC;discussed below) and the CCOGC. Canine Cancer Tissue Arrays: In collaboration with Dr. Stephen Hewitt (CCR - Tissue Array Project), a number of robust canine cancer tissue arrays have been developed. These arrays include outcome linked canine lymphoma, outcome linked canine osteosarcoma, outcome linked nasal carcinoma, mammary cancer, prostate cancer ,and a multi-tumor canine tissue array. These array reagents have and will be useful for the identification of therapeutic targets in canine cancers, and the study of cancer and metastasis biology. 2. Develop multi-center collaborative network with extramural comparative oncology programs. Within this network design, implement and manage pre-clinical trials involving pet animals that will evaluate novel therapeutic strategies for cancer;Comparative Oncology Trial Consortium: The Comparative Oncology Program has used its neutral leadership position to bring together twenty top-notch schools of veterinary medicine to collaborate as a multi-center clinical trial network. This network works together through the leadership of the Comparative Oncology Program to offer the pharmaceutical industry, other parts of the National Cancer Institute, and the broader academic community the opportunity to inform their cancer drug development paths by using naturally occurring cancers in dogs as models for drug development. The Comparative Oncology Trials Consortium has completed seven clinical trials thus far. A manuscript detailing the development of rapamycin in canine osteosarcoma was published in PLoSONE (COTC003 and COTC008). In addition in FY 2010 there have been 3 active COTC trials open for accrual. 3. Increase the awareness of the appropriate use of naturally occurring cancer models within the cancer research community. Both Drs. Khanna and Paoloni are frequently invited speakers asked to present the attributes of the comparative approach to drug development to both academic and industry groups.

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National Cancer Institute (NCI)
Animal Research Infrastructure Intramural Research (ZIG)
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Paoloni, Melissa; Webb, Craig; Mazcko, Christina et al. (2014) Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials. PLoS One 9:e90028
Kirby, G M; Mackay, A; Grant, A et al. (2011) Concentration of lipocalin region of collagen XXVII alpha 1 in the serum of dogs with hemangiosarcoma. J Vet Intern Med 25:497-503
Briggs, Joseph; Paoloni, Melissa; Chen, Qing-Rong et al. (2011) A compendium of canine normal tissue gene expression. PLoS One 6:e17107
Vail, D M; Michels, G M; Khanna, C et al. (2010) Response evaluation criteria for peripheral nodal lymphoma in dogs (v1.0)--a Veterinary Cooperative Oncology Group (VCOG) consensus document. Vet Comp Oncol 8:28-37
Gordon, Ira K; Khanna, Chand (2010) Modeling opportunities in comparative oncology for drug development. ILAR J 51:214-20
Paoloni, Melissa C; Mazcko, Christina; Fox, Elizabeth et al. (2010) Rapamycin pharmacokinetic and pharmacodynamic relationships in osteosarcoma: a comparative oncology study in dogs. PLoS One 5:e11013
Khanna, Chand; Gordon, Ira (2009) Catching cancer by the tail: new perspectives on the use of kinase inhibitors. Clin Cancer Res 15:3645-7
Paoloni, Melissa; Davis, Sean; Lana, Susan et al. (2009) Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression. BMC Genomics 10:625
Khanna, Chand; London, Cheryl; Vail, David et al. (2009) Guiding the optimal translation of new cancer treatments from canine to human cancer patients. Clin Cancer Res 15:5671-7
Gordon, Ira; Paoloni, Melissa; Mazcko, Christina et al. (2009) The Comparative Oncology Trials Consortium: using spontaneously occurring cancers in dogs to inform the cancer drug development pathway. PLoS Med 6:e1000161

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