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 ( Its 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. A manuscript detailing the creation of the COTC PD Core infrastructure was published in The Veterinary Journal. Since its inception the COTC PD Core has been used to support 4 COTC trials. The COTC PD Core completed its 3rd RFP. 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 2011-12: 1) Manuscript 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. PLoS One. 2011;6(5):e17107. Epub 2011 May 31. 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. Canine Cancer Biospecimen Repository: A biospecimen repository of frozen, and formalin fixed tissues from 1800 dogs with cancer has been established through a contract with Fisher Bioservices. In 2013 the CCOGC began releasing tissues based on scientific merit. To date over 1000 samples have been released . 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, and a multi-tumor canine tissue array. Version 2.0 of the multi-tumor canine tissue array is under development. 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/and are used to assist with pre-clinical studies for future COTC efforts. 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 ten clinical trials thus far and currently has two open trials. COTC016 was a personalized medicine based trial to assess the timeline for prospective tumor tissue collection and histopathologic/molecular profiling. It was published in PLOS One in Q1 2014. COTC018: The evaluation of iniparib in dogs with cancer in collaboration with Sanofi-Aventis was completed in 2013. The manuscript for COTC018 will be submitted to PLOS One in Q3 2014. COTC007b: The preclinical evaluation of 3 indenoisoquinolines, in collaboration with NCI-DTP, is ongoing and expected to be completed in Q4 2014. In Q3 2014, study COTC020: Evaluation of orally administered mTOR inhibitor Rapamycin in dogs with osteosarcoma opened for accrual. Study COTC020 is pilot study for a larger adjuvant study in dogs with osteosarcoma evaluating oral rapamycin. This adjuvant study will be part of the 5-5-5 Study. The 5-5-5 study, with support from Morris Animal Foundation and the Children's Oncology Group, will conduct clinical trials in pet dogs with osteosarcoma to assess novel therapies that show promise for the treatment of canine and human bone cancers. The goal is five clinical trials, in five years at a total of 5 million dollars. Oversight of the 5-5-5 will come from a Scientific Advisory Board. Dr. Amy LeBlanc, newly appointed Deputy Director of the Comparative Oncology Program, serves on the SAB 3. Increase the awareness of the appropriate use of naturally occurring cancer models within the cancer research community. Both Drs. Khanna and LeBlanc are frequently invited speakers asked to present the attributes of the comparative approach to drug development to both academic and industry groups. A new brain tumor initiative is currently underway. A meeting is being planned in 2015 to bring together leaders in the field of brain tumors from both the human and veterinary side. A workshop titled """"""""The Role of Clinical Studies for Pets with Naturally Occurring Tumors in Translational Cancer Research"""""""" is currently being planned for 2015 at the Institute of Medicine (IOM).

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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; 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
Withrow, Stephen J; Khanna, Chand (2009) Bridging the gap between experimental animals and humans in osteosarcoma. Cancer Treat Res 152:439-46
Abdeen, Ayesha; Chou, Alexander J; Healey, John H et al. (2009) Correlation between clinical outcome and growth factor pathway expression in osteogenic sarcoma. Cancer 115:5243-50

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