Jan 03, 2016
OsteosarcomaNormal Tissues
Human Dog
Companion Animal Cancer Models Large outbred Animals Strong Genetic similarities to Humans
Naturally Occurring cancers Immune competant and syngeneic Relevant Tumor Histology/Genetics Relevant Response Profiles to Conventional Chemotherapy
Tumor Heterogeneity Metastasis Biology Recurrence/Resistance
Cancer IN Companion Animals 65 Million Companion Animals in the US
4 million pet dogs diagnosed with cancer each year
Pet owners seek advanced care for their pets
Comparative Oncology
TO PROVIDE OPPORTUNITIES TO INCLUDE NATURALLY OCCURRING CANCER MODELS IN THE STUDY OF CANCER BIOLOGY AND THERAPY
The CCR - Comparative Oncology Program
•Develop essential reagent kit for the study of comparative models in translational and biology-based research;
•Develop multicenter 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;
•Increase the awareness of the appropriate use of naturally occurring cancer models within the cancer research community;
Resources and Reagents: opportunities for Layered
Translation
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Human Serum
Canine Serum #1
Canine Serum #2
Canine Serum #3
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Comparative Oncology Trials Consortium (COTC)
Draft Trial Overview
-2-3 Page Summary
- Internal Review
Trial Overview Board
-CCR/CTEP/DTP Members
- Focus on value of dog trial to development path
COTC Consortium Members
-Review Trial Overviews
Solicit Ad Hoc Community Reviews
-Individuals/Groups likely to be involved in clinical development
Re-draft Re-draftRe-draft
Approval Package
Decision Package for CCR Directors
Solicit Ad Hoc Community to Review Full Protocol (JDC)
-Individuals/Groups likely to be involved in clinical development and/or data management
COTC Consortium Members
-Review Full Protocol
Commence Trial
Collaboration Initiated
-Pharma
-NCI CCR-COP
-Academia
Re-draft
Trial Review Process: Effort to ensure integration
Integration of a Comparative Approach
ActivityToxicity
PharmacokineticsPharmacodynamics
DoseRegimenScheduleBiomarkers
Responding HistologiesCombination therapies
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Small AnimalPreclinical Phase III Human
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Tumor-BearingDog Studies
Phase II HumanClinical Trials
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Phase I HumanClinical Trials
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Tumor-BearingDog Studies
Non-Human PrimateBeagle Dog
New Cancer Drug
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Large Pharma
Merck Status: CDA in place, meeting to discuss collaborations has
been scheduled for early January 2006.
Astrazeneca Status: Meeting is planned for mid-November to discuss a trial
in pet dogs.
Small Pharma/Biotech
Genzyme Status: CRADA meeting and presentation completed.
Locus Pharmaceuticals Status: CDA has been completed and a Trial Overview is being
drafted.
Academia/Biotech
SemaCo Status: CDA IN PLACE, in vitro evaluation underway (T Olgios in canine OSA
cell lines)
Colando Pharmaceuticals Status: Currently validating their anti-RRM2 antibody in canine normal and
tumor tissues by Western and Immunohistochemical analysis.
Center for Cancer Research
Radiation Oncology (Jim Mitchel) Tempol Evaluation of intravenous Tempol in pet dogs receiving fractionated
radiation therapy in dogs with head and neck cancer Status - Trial overview in second review
Surgery Branch (Steve Libutti) Phage Delivery of TNF- Evaluation of RGD Targeted Delivery of Phage Expressing TNF- To Tumor
Bearing Dogs Status - Trial approved for initiation
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NewsNature Medicine 11, 1018 (2005) Published online: 28 September 2005; | doi:10.1038/nm1005-1018a
Cancer researchers usher in dog days of medicineGeorge S Mack
Columbia, South Carolina
After thousands of years of friendship, man and dog will soon be working together to advance drug discovery. As part of a new comparative-oncology program at the US National Cancer Institute, researchers are set to begin drug trials in dogs that aim to bridge the gap between preclinical drug studies and effects of the same drug in people.
Two multicenter trials, set to begin in early 2006, will evaluate new therapeutic approaches for cancer in dogs, says program chief Chand Khanna, a veterinary oncologist at the institute's Center for Cancer Research.
"It turns out that many cancers, such as lymphoma, melanoma and osteosarcoma, are well represented in pet dogs," Khanna says. "The dogs will help us prioritize the agents that go into human clinical trials and help make those trials more efficient."
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Wall Street Journal July 7, 2005
Nature Medicine October 2005
The Good News…We have arrived. Now we must deliver
Acknowledgments
Comparative Oncology ProgramCCR, National Cancer Institute Melissa Paoloni
Christina Mazcko
Katherine Hansen
Tumor and Metastasis BiologySection, PEDIATRIC ONCOLOGY BRANCH
CCR, National Cancer Institute Ling Ren
Arnulfo Mendoza
Jessica Cassavaugh
Rachel Blackwood
Sung-Hyeok Hong
Lauren Shapiro
Ben Bruce
Rachel Newman
Gaurav Khanna
AcknowledgmentsMolecular Oncology Section
Pediatric Oncology BranchCCR, National Cancer Institute Xiaolin Wan
Choh Yeung
Lee Helman
Tissue Array Research Project (TARP), CCRStephen HewittKimberly Parker
Biomedical Proteomics Program, CCRLiRoung YuMing ZhouTim Veenstra
Cornell UniversityAnthony Bretscher
Columbia UniversityCharles PowellAlain Borczuk
University of MichiganEvan Keller
University of UmeaGoran Landberg
State University of OhioMark Berryman
LCMB, CCR, National Cancer Institute Yanlin Yu
Glenn Merlino
Cancer Genetics Branch, NHGRIKristin BairdPaul Meltzer
Oncogenomics Section, POB, NCIJaved Khan
Carcinogenesis/Prevention, CCRNancy Colburn