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 (http://ccr.nci.nih.gov/resources/cop/). 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. In FY 2011-12 the COTC PD Core was used to support 3 different COTC trials. 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 (http://ccr.cancer.gov/resources/cop/scientists/resource_antibody.asp) (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 respository of frozen, and formalin fixed tissues from dogs with cancer has been established through a contract with Fisher Bioservices. In 2012, the Repository has currently completed tissue collection (1800 patient samples) and is set to open for release. 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/andare 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. COTC016 was a personalized medicine based trial to assess the timeline for prospective tumor tissue collection and histopathologic/molecular profiling. It was completed in FY2011. Two additional trials opened in 2012: COTC007b: The preclinical evaluation of 3 indenoisoquinolines in collaboration with NCI-DTP and COTC018: The evaluation of iniparib in dogs with cancer in collaboration with Sanofi-Aventis. COTC018 was completed and closed in 2013. COTC007b is ongoing and expected to be completed in 2014. 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Animal Research Infrastructure Intramural Research (ZIG)
Project #
1ZIGBC010569-10
Application #
8763826
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2013
Total Cost
$336,493
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
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
Phillips, Brenda; Powers, Barbara E; Dernell, William S et al. (2009) Use of single-agent carboplatin as adjuvant or neoadjuvant therapy in conjunction with amputation for appendicular osteosarcoma in dogs. J Am Anim Hosp Assoc 45:33-8
Paoloni, Melissa C; Tandle, Anita; Mazcko, Christina et al. (2009) Launching a novel preclinical infrastructure: comparative oncology trials consortium directed therapeutic targeting of TNFalpha to cancer vasculature. PLoS One 4:e4972
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
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; Khanna, Chand (2008) Translation of new cancer treatments from pet dogs to humans. Nat Rev Cancer 8:147-56
Kisseberth, W C; Vail, D M; Yaissle, J et al. (2008) Phase I clinical evaluation of carboplatin in tumor-bearing cats: a Veterinary Cooperative Oncology Group study. J Vet Intern Med 22:83-8