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COTC Questionnaire
Completed 2008

This questionnaire was designed to assess the use and associated adverse events of human oncology drugs within the practice of veterinary oncology. The questionnaire is divided into three sections (off label use of approved human drugs, agents in early human clinical trials, general questions) and all answers are tallied in red. The questionnaire was distributed to seventeen COTC institutions and was completed and returned by nine. The results from the questionnaire have been used in several presentations and recent publications. For additional information please contact Christina Mazcko at mazckoc@mail.nih.gov.

Publications

Several advances in the field of cancer have been made through a comparative oncology approach. Recent national attention has highlighted the comparative oncology program:

[Updated] Translation Of New Cancer Treatments From Pet Dogs To Humans.
Nature Reviews Cancer. February 2008.

Cancer Clues from Pet Dogs.Scientific American. December 2006.

In Trials for New Cancer Drugs, Family Petes are Benefiting, Too. November 2006.

The Dog as a Cancer Model. Nature Biotechnology. September 2006.

Wall Street Journal: Cancer Strides for Dogs Assist Human Therapy

Clinical Trials Going to the Dogs: Canine Program to Study Tumor Treatment, Biology. Journal of the National Cancer Institute, Vol. 98, No. 3, February 1, 2006

Cancer researchers usher in dog days of medicine. Nat Med 11: 1018, 2005.

The Dog as a Cancer Model. Nature Biotechnology, Vol. 26, No.9, September 2005.

Comparative oncologists study naturally occurring pet cancer to:

Understand environmental risks for human cancer.Companion animals may represent sentinels for environmental risk factors for cancer. Furthermore, these models may be helpful for the study of agents that may prevent cancers.

• Hargis AM, Thomassen RW. Animal model: solar dermatosis (keratosis) and solar dermatosis with squamous cell carcinoma. Am J Pathol. 1979 Jan; 94(1):193-6.
• Reif JS, Dunn K, Ogilvie GK, et al. Passive smoking and canine lung cancer risk. Am J Epidemiol. 1992 Feb 1; 135(3): 234-9.
• Glickman LT, Schofer FS, McKee LJ, et al. Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. J Toxicol Environ Health. 1989; 28(4): 407-14.
• Hayes HM, Tarone RE, Cantor KP. Case-control study of canine malignant lymphoma: positive association with dog owner’s use of 2, 4 dichlorophenoxyacetic acid herbicides. J Natl Cancer Inst. 1991 Sep 4; 83(17): 1226-31.
• Waters DJ, Hayden DW, Bell FW, et al. Prostatic intraepithelial neoplasia in dogs with spontaneous prostate cancer. Prostate. 1997 Feb 1; 30(2): 92-7.
• Bukowski JA, Wartenberg D, Goldschmidt M. Environmental causes for sinonasal cancers in pet dogs and their usefulness as sentinels of indoor cancer risk. J Toxicol Environ Health A. 1998 Aug 7; 54(7): 579-91.

Examine genetic/familial determinants for cancer predispositions.The study of cancer genetics can be simplified by studies of cancer risk in breeds of dogs and within families of dogs. Cancer genes identified in dogs have been shown to be relevant in human familial cancers. This work will be enhanced with the progress of the canine genome project.

• Onions DL. A prospective survey of familial canine lymphosarcoma. J Natl Cancer Inst. 1984 Apr; 72(4): 909-12.
• Szabo CI, Wagner LA, Francisco LV, et al. Human, canine and murine BRCA1 genes: sequence comparison among species. Hum Mol Genet. 1996 Sep; 5(9): 1289-98.
• Schafer KA, Kelly G, Schrader R, et al. A canine model of familial mammary gland neoplasia. Vet Pathol. 1998 May; 35(3): 168-77.
• Jonasdottir TJ, Mellersh CS, Moe L, et al. Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs. Proc Natl Acad Sci U S A. 2000 Apr 11; 97(8): 4132-7.
• Ostrander EA, Comstock KE. The domestic dog genome. Curr Biol. 2004 Feb 3; 14(3): R98-9.
• Lindblad-Toh K. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature. 2005 Dec; 438(8): 803-819.

Improve our understanding of cancer biology and to add biological relevance to genomics data in experimental model systems.The availability of tumor samples from large populations of dogs contributes to their value to the study of cancer biology. The availability of molecular techniques and information from the canine genome project will enhance opportunities to study cancer biology that is informative for human disease in companion animals.

• London CA, Galli SJ, Yuuki, et al. Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit. Exp Hematol. 1999 Apr; 27(4): 689-97.
• Prescott DM, Charles HC, Poulson JM, et al. The relationship between intracellular and extracellular pH in spontaneous canine tumors. Clin Cancer Res. 2000 Jun; 6(6): 2501-5.
• Thomas R, Fiegler H, Ostrander EA, et al. A canine cancer-gene microarray for CGH analysis of tumors. Cytogenet Genome Res. 2003; 102(1-4): 254-60.
• Catchpole B, Gould SM, Kellett-Gregory LM, et al. Development of a multiple-marker polymerase chain reaction assay for detection of metastatic melanoma in lymph node aspirates of dogs. Am J Vet Res. 2003 May; 64(5): 544-9.
• Khanna C, Wan X, Bose S, et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004 Feb; 10(2): 182-6.

Evaluate novel therapeutic strategies.In addition to techniques such as chemotherapy, surgery, and radiation, approaches such as anti-angiogenesis, immunotoxins, and general immunotherapy are now being used to fight cancer. These novel treatments were tested first in animals.

• Kurzman ID, MacEwen EG, Rosenthal RC, et al. Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin. Clin Cancer Res. 1995 Dec; 1(12): 1595-601.
• Andrawiss M, Opolon P, Benihoud K, et al. Adenovirus-mediated gene transfer in dog prostate: a preclinical study of a relevant model system for gene therapy of human prostatic cancer. Prostate Cancer Prostatic Dis. 1999 Jan; 2(1): 25-35.
• Knapp DW, Glickman NW, Widmer WR, et al. Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Cancer Chemother Pharmacol. 2000; 46(3): 221-6.
• Khanna C, Prehn J, Hayden D, et al. A randomized controlled trial of octreotide pamoate long-acting release and carboplatin versus carboplatin alone in dogs with naturally occurring osteosarcoma: evaluation of insulin-like growth factor suppression and chemotherapy. Clin Cancer Res. 2002 Jul; 8(7): 2406-12.
• Pryer NK, Lee LB, Zadovaskaya R, et al. Proof of target for SU11654: inhibition of KIT phosphorylation in canine mast cell tumors. Clin Cancer Res. 2003 Nov 15; 9(15): 5729-34.
• Khanna C, Vail DM. Targeting the lung: preclinical and comparative evaluation of anticancer aerosols in dogs with naturally occurring cancers. Curr Cancer Drug Targets. 2003 Aug; 3(4): 265-73.
• Bergman PJ, McKnight J, Novosad A, et al. Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial. Clin Cancer Res. 2003 Apr; 9(4): 1284-90.
• Hansen K, Khanna C. Spontaneous and genetically engineered animal models: use in preclinical cancer drug development. Eur J Cancer. 2004 Apr; 40(6): 858-80.