Comparative Oncology Program:

Specific Aim 1:
Education/Outreach
An early goal of the COP will be to provide information on the availability and value of naturally occurring cancer models to CCR faculties and investigators and the broader cancer research community. The use of naturally occurring cancers in the study of cancer biology, genetics and therapy is still outside the consideration of most researchers. The significance of these models is self evident once their existence and availability are described. As part of this specific aim the COP will facilitate scientific collaborations that will utilize these naturally occurring cancer models. Both parts of this specific aim, education and collaborations, will be pursued in tandem through the following efforts:
• CCR-COP Website – designed within the CCR Website
• Interaction with CCR Faculties
• Journal of Veterinary and Comparative Oncology
• Invited publications (Link to publications section of COP website – added at later date)
• Participation in National Meetings
• Quarterly Seminar Series – Comparative Oncology

Specific Aim 2.
Characterization of models (Genomic and Proteomic)
Extensive characterizations of spontaneous cancer models have been undertaken over the past 20 years. This work includes epidemiology, basic biology, tumor pathology, and response to therapy. Recent efforts have been directed at defining these models at the molecular and proteomic level. To most effectively utilize these models in clinical trials using targeted therapeutics, it will be essential for this more advanced model characterization to continue.

Work involved with this specific aim will be undertaken through a COP laboratory within the CCR and through collaborations with active comparative oncology groups in the extramural program. To facilitate this work a canine cancer tissue bank is under construction within the CCR (central CCR tissue repository - under development). Work from within the COP laboratory and from other investigators will be made available through the COP website.

It is expected that the COP will be to work with the CCR and other NIH faculty, using existing infrastructure, to develop a canine oligo-microarray, histology specific tissue microarrays, and to optimize proteomic technologies for the use of canine samples. These reagent resources will allow the ongoing characterization of Comparative Oncolgoy models. This effort will constitute the basis of validation for these models and will add significant value to existing programs involved in Comparative Oncology. The COP will use these technologies to focus on canine osteosarcoma, canine non-Hodgkins (NH) lymphoma and canine prostate cancer.

Specific Aim 3.
Translational investigations
The COP will facilitate collaborations between CCR investigators, the pharmaceutical industry, and existing comparative and veterinary oncology groups such that the efficacy, safety and biology of novel cancer therapies may be examined in spontaneous animal models. Preclinical trials will be designed to include multiple layers of translation, i.e. translation of drug efficacy, translation of validated pharmacodynamic endpoints, translation of functional imaging strategies, translation of integrated bioinformatics systems, translation of clinical genomic/proteomic platforms.

Spontaneous cancer models will greatly enhance the application and delivery of new knowledge to the management of human patients. The COP will serve as a resource in the design and implementation of clinical trials and in the procurement and maintenance of tissue resources in the COP tissue bank. Studies in tumor biology using spontaneous tumors will generate a broader understanding of how novel therapies may act and may be best used for future human patients.

Specific Aim 4.
Comparative Oncology Training Program.
In order for comparative approaches to cancer research to become more widely and appropriately used it is essential that individuals involved in comparative oncology be well trained. The COP will provide an outstanding educational environment for veterinary oncologists and other investigators in tumor and metastasis biology, genetics, and drug development.

The CCR - Comparative Molecular Pathology Program (Dr. Mark Simpson) will provide the structure for the training of future comparative oncologists. The COP will help to identify and recruit top-level candidates to the Comparative Molecular Pathology Program. The COP will also offer its laboratory and clinical trial programs to the Comparative Molecular Pathology Training Program. The primary goal will be to provide high-level training in basic science to individuals with experience and interest in comparative oncology.