A central mission of the Center for Cancer Research (CCR), National Cancer Institute (NCI) is the development and delivery of novel cancer treatment strategies for cancer patients. A significant hurdle in the translation of information from the laboratory to the clinic is the availability of appropriate preclinical cancer models. Through a number of new initiatives the CCR has created an essential infrastructure to facilitate the translational research process. An example of this effort is the CCR - Comparative Oncology Program (http://ccr.nci.nih.gov/resources/cop/). Comparative Oncology refers to the study of naturally occurring cancers, primarily in companion animals. The efforts of the CCR-COP have been strategically aligned with several ongoing projects within the CCR, within existing programs in extramural Comprehensive Cancer Centers, and with close attention to the needs and interests of the pharmaceutial and biotechnology communities. Accordingly, all CCR-COP efforts have been collaborative in nature, lead by the CCR-COP, and have resulted in value within several groups. In the two years since the CCR-COP inception, significant milestones have been attained, within all three core sub-project areas of interest. Using its neutral leadership position, the CCR-COP has brought together a broad representation of parties (academic, industry, government) focused on the genetics and biology of cancer in dogs (Comparative Oncology and Genomics Consortium - CCOGC). The CCOGC has embarked on an effort to build an infrastructure necessary for the study and characterization of canine cancers using newly developed genomic and biological tools. Working with the CCOGC members, the CCR-COP has launched a National Canine Biospecimen Repository. This repository is housed within the CCR and has established a CaBIG compliant bioinformatics system to collect, track, and retrieve tissues. Interest in the tissue assets of the repository from the cancer research community, including both academic and industry groups, has already been very strong. In parallel the CCR-COP has worked closely with several groups to develop and optimize techniques that allow the analysis of canine cancers using platforms common to the cancer research community (microarray, proteomics, antibody screens, tissue arrays). Using these techniques the CCR-COP has begun to define important similarities and differences between canine and human cancers. These data will allow appropriate questions to be asked of these complex spontaneously arising cancer models. In totem, the development of a biologic reagent kit and infrastructure has been developed for the study of cancer in dogs as models. In order to use canine cancer models in translational drug development studies, the CCR-COP has united members of extramural NCI Comprehensive Cancer Centers, and other unaffiliated schools of veterinary medicine to collaborate within a multi-center clinical trial network called the Comparative Oncology Trial Consortium (COTC). The primary goals of the COTC is to offer the pharmaceutical industry, the National Cancer Institute itself, and the broader academic community the opportunity to inform their cancer drug development paths by using naturally occurring cancers in dogs as models. Agreements that facilitate the transfer of agents from sponsoring entities (e.g., pharmaceutical industry) through the CCR-COP to members of the COTC have been executed. The first trial through the COTC was completed in the spring of 2006. Significant, and growing interest in future trials has been expressed by large pharma, the biotechnology community, and academic groups involved in cancer drug development. The 11th trial of the COTC was initiated in FY2008. Essentially all efforts of the CCR-COP have been conducted through collaborative efforts. These collaborations have included intramural NIH investigators and programs, extramural academic groups, the pharmaceutical industry, and patient aligned cooperative groups including the Children's Oncology Group, and the Sarcoma Alliance for Research Cooperation. It has been a priority of the CCR-COP to engage these groups in the definition and execution of its goals. The result has been a rapid, flexible and responsive form of team science. The CCR-COP has worked closely with the CCR Technology Transfer Branch to define and establish mechanisms that allow interaction and collaborations with both academic and for-profit partners. This has included a Memorandum of Understanding between members of the Comparative Oncology and Genomics Consortium and the CCR-COP for the transfer of tissues destined to be part of the National Canine Biospecimen Repository. Memoranda of Understanding have also been executed between the CCR-COP and institutional members of the Comparative Oncology Trials Consortium with parallel Material Transfer Agreements allowing interaction with members of the pharmaceutical community. Material transfer agreements are currently in place with several pharmaceutical and biotechnology companies interested in evaluating novel cancer drugs through our comparative approach.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010569-05
Application #
7733090
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2008
Total Cost
$460,555
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Guimond, Martin; Freud, Aharon G; Mao, Hsiaoyin C et al. (2010) In vivo role of Flt3 ligand and dendritic cells in NK cell homeostasis. J Immunol 184:2769-75
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
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
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
Khanna, Chand; Gordon, Ira (2009) Catching cancer by the tail: new perspectives on the use of kinase inhibitors. Clin Cancer Res 15:3645-7
Khanna, Chand (2008) Novel targets with potential therapeutic applications in osteosarcoma. Curr Oncol Rep 10:350-8
Paoloni, Melissa C; Khanna, Chand (2007) Comparative oncology today. Vet Clin North Am Small Anim Pract 37:1023-32;v
Khanna, Chand; Lindblad-Toh, Kerstin; Vail, David et al. (2006) The dog as a cancer model. Nat Biotechnol 24:1065-6
Khanna, Chand; Hunter, Kent (2005) Modeling metastasis in vivo. Carcinogenesis 26:513-23
Hansen, K; Khanna, C (2004) Spontaneous and genetically engineered animal models; use in preclinical cancer drug development. Eur J Cancer 40:858-80