Dogs: Active Role Model for Cancer Studies—A Review


Many studies have been done and many results have been established for studying cancers in human and the ways of treating it. However, one thing that remains relevant is the study model that is used to diagnose, cure or conclude treatment methods for human cancers. The scientists have tried some ways to link the data and tried to analyze the malicious disease in various animal models in order to solve the problem for humans. Out of all the models, scientists have preferred dogs as the most suitable model and conducted studies on them. Our article will review the reason for preferences given to dog as a study model and what the previous studies have tried to conclude by considering the dreaded disease in dogs. Our article has focused on most of the recent observations and tried to elucidate the reasons/preferences for studying cancer disease in dogs (scientific name; Canis Lupus familiaris). We will also talk about the idea of comparative oncology programs that many centers adapt in order to study the disease called cancer.

Share and Cite:

S. Hawai, M. Al-Zayer, M. Ali, Y. Niu, A. Alawad, M. Aljofan, A. Aljarbou and S. Altuwaijri, "Dogs: Active Role Model for Cancer Studies—A Review," Journal of Cancer Therapy, Vol. 4 No. 5, 2013, pp. 989-995. doi: 10.4236/jct.2013.45113.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] B. Leder, “Breast Cancer in Dogs,” 2009.
[2] J. Ferlay J, H. R. Shin, F. Bray, D. Forman, C. Mathers and D. M. Parkin, “Globcan 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10,” 2010., accessed on day/month/year
[3] Marisa Weiss, et al., “US Breast Cancer Statistics,” 2012. symptoms/understand_bc/ statistics
[4] M. H Tirgan, “A Short Review on Breast Cancer,” 1996-2011.
[5] D. Smith, C. Broadhead, G. Descotes, et al., “Preclinical Safety Evaluation Using Nonrodent Species: An Industry/Welfare Project to Minimize Dog Use,” The ILAR Journal, Vol. 43, Supplement S39-S42, 2002, pp. 39-42.
[6] E. G. McEwen, “Spontaneous Tumors in Dogs and Cats: Models for the Study OF Cancer Biology and Treatment,” Cancer and Metastasis Reviews, Vol. 9, No. 2, 1990, pp. 125-136. doi:10.1007/BF00046339
[7] K. A. Hahn, L. Bravo, W. H. Adams and D. L. Frazier, “Naturally Occurring Tumors in Dogs as Comparative Models for Cancer Therapy Research,” In Vivo, Vol. 8, No. 1, 1994, pp. 133-143.
[8] D. M. Vail and E.G. McEwen, “Spontaneously Occurring Tumors of Companion Animals as Models for Human Cancer,” Cancer Investigation, Vol. 18, No. 18, 2000, pp. 781-792. doi:10.3109/07357900009012210
[9] L. Nasir, P. Devlin, T. Mckevitt, et al., “Telomere Lengths and Telomerase Activity in Dog Tissues: A Potential Model System to Study Human Telomere and Telomerase Biology,” Neoplasia, Vol. 3, No. 4, 2001, pp. 351-359. doi:10.1038/sj.neo.7900173
[10] T. Vargo-Gogola and J. Rosen, “Modeling Breast Cancer: One Size Does Not Fit All,” Nature reviews Cancer, Vol. 7, No. 9, 2007, pp. 659-672. doi:10.1038/nrc2193
[11] S. Nandi, R. C. Guzman and J. Yang, “Hormones and Mammary Carcinogenesis in Mice, Rats, and Humans: A Unifying Hypothesis,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 9, 1995, pp. 3650-3657. doi:10.1073/pnas.92.9.3650
[12] F. Balkwill, K. A. Charles and A. Mantovani, “Smoldering and Polarized Inflammation in the Initiation and Promotion of Malignant Disease,” Cancer Cell, Vol. 7, No. 3, 2005, pp. 211-217. doi:10.1016/j.ccr.2005.02.013
[13] S. Goswami, E. Sahai, J. B. Wyckoff, M. Cammer, D. Cox, F. J. Pixley, E. R. Stanley, J. E. Segall and J. S. Condeelis, “Macrophages Promote the Invasion of Breast Carcinoma Cells via a Colony Stimulating Factor-1/Epidermal Growth Factor Paracrine Loop,” Cancer Research, Vol. 65, No. 12, 2005, pp. 5278-5283. doi:10.1158/0008-5472.CAN-04-1853
[14] K. L. Schwertfeger, J. M. Rosen and D. A. Cohen, “Mammary Gland Macrophages: Pleiotropic Functions in Mammary Development,” Journal of Mammary Gland Biology and Neoplasia, Vol. 11, No. 3-4, 2006, pp. 229-238.
[15] J. W. Pollard, “Role of Colony-Stimulating Factor-1 in Reproduction and Development,” Molecular Reproduction and Development, Vol. 46, No. 1, 1997, pp. 54-60. doi:10.1002/(SICI)1098-2795(199701)46:1<54::AID-MRD9>3.0.CO;2-Q
[16] R. C. Hovey, T. B. McFadden and R. M. Akers, “Regulation of Mammary Gland Growth and Morphogenesis by the Mammary Fat Pad: A Species Comparison,” Journal of Mammary Gland Biology and Neoplasia, Vol. 4, No. 1, 1999, pp. 53-68. doi:10.1023/A:1018704603426
[17] N. Erin, W. Zhao, J. Bylander, G. Chase and G. Clawson, “Capsaicin-Induced Inactivation of Sensory Neurons Promotes a More Aggressive Gene Expression Phenotype in Breast Cancer Cells,” Breast Cancer Research and Treatment, Vol. 99, No. 3, 2006, pp. 351-364. doi:10.1038/nbt0906-1065b
[18] C. Khanna, K. Lindblad-Toh, D. Vail, C. London, P. Bergman, et al., “The Dog as a Cancer Model,” Nature Biotechnology, Vol. 24, No. 9, 2006, pp. 1065-1066. doi:10.1038/nbt0906-1065b
[19] A. L. Shearin and E. A. Ostrander, “Leading the Way: Canine Models of Genomics and Disease,” Disease Models & Mechanisms, Vol. 3, No. 1-2, 2010, pp. 27-34. doi:10.1242/dmm.004358
[20] R. T. Bronson, “Variation in Age at Death of Dogs of Different Sexes and Breeds,” American Journal of Veterinary Research, Vol. 43, No. 11, 1982, pp. 2057-2059.
[21] L. E. Maquat, “Defects in RNA Splicing and the Consequence of Shortened Translational Reading Frames,” The American Journal of Human Genetics, Vol. 59, No. 2, 1996, pp 279-286.
[22] C. Zandonella, “Cancer Collaboration Could Someday Help Dogs and Their Humans,” 2012.
[23] I. K. Gordon and C. Khanna, “Modeling Oppurtunities in Comparative Oncology for Drug Development,” The ILAR Journal, Vol. 51, No. 3, 2010, pp. 214-220. doi:10.1093/ilar.51.3.214
[24] J. Modiano, “Genetic Cancer Link between Humans and Dogs Discovered,” 2008.
[25] J. David, W. Waters and K. Wildasin, “The Vital Importance of Comparative Oncology: Cancer Clues from Dogs,” 2006.
[26] K. Lindblad-Toh, C. M. Wade, T. S. Mikkelsen, E. K. Karlsson, D. B. Jaffe, et al., “Genome Sequence, Comparative Analysis and Haplotype Structure of the Domestic Dog,” Nature, Vol. 438, No. 7069, 2005, pp. 803-819. doi:10.1038/nature04338
[27] H. G. Parker and E. A. Ostrander, “Canine Genomics and Genetics: Running with the Pack,” PLOS Genetics, Vol. 1, No. 5, 2005, p. e58. doi:10.1371/journal.pgen.0010058
[28] J.A. Holzwarth, R. P. Middleton, M. Roberts, R. Mansourian, F. Raymond, et al., “The Development of a HighDensity Canine Microarray,” Journal of Heredity, Vol. 96, No. 7, 2005, pp. 817-820.
[29] M. Paoloni and C. Khanna, “Translation of New Cancer Treatments from Pet Dogs to Humans,” Nature Reviews Cancer, Vol. 8, No. 2, 2008, pp. 147-156. doi:10.1038/nrc2273
[30] R. Thomas, A. Scott, C. F. Langford, S. P. Fosmire, C. M. Jubala, et al., “Construction of a 2-Mb Resolution BAC Microarray for CGH Analysis of Canine Tumors,” Genome Research, Vol. 15, No. 12, 2005, pp. 1831-1837. doi:10.1101/gr.3825705
[31] M. M. Hoffman and E. Birney, “Estimating the Neutral Rate of Nucleotide Substitution Using Introns,” Molecular Biology and Evolution, Vol. 24, No. 2, 2007, pp 522-531. doi:10.1101/gr.3825705
[32] M. Breen and J. F. Modiano, “Evolutionarily Conserved Cytogenetic Changes in Hematological Malignancies of Dogs and Humans—Man and His Best Friend Share More Than Companionship,” Chromosome Research, Vol. 16, No. 1, 2008, pp. 145-154. doi:10.1007/s10577-007-1212-4
[33] R. Thomas, K. C. Smith, E. A. Ostrander, F. Galibert and M Breen, “Chromosome Aberrations in Canine Multicentric Lymphomas Detected with Comparative Genomic Hybridization and a Panel of Single Locus Probes,” British Journal of Cancer, Vol. 89, No. 8, 2003, pp. 1530-1537. doi:10.1038/sj.bjc.6601275
[34] A. Rungsipipat, S. Tateyama, R. Yamaguchi, K. Uchida, N. Miyoshi and T. Hayashi, “Immunohistochemical Analysis of c-yes and c-erbB-2 Oncogene Products and p53 Tumor Suppressor Protein in Canine Mammary Tumors,” Journal of Veterinary Medical Science, Vol. 61, No. 1, 1999, pp. 27-32. doi:10.1292/jvms.61.27
[35] A. Setoguchi, T. Sakai, M. Okuda, K. Minehata, M. Yazawa, T. Ishizaka, T. Watari, R. Nishimura, N. Sasaki, A. Hasegawa and H. Tsujimoto, “Aberrations of the p53 Tumor Suppressor Gene in Various Tumors in Dogs,” American Journal of Veterinary Research, Vol. 62, No. 3, 2001, pp. 433-439. doi:10.2460/ajvr.2001.62.433
[36] S. Haga, M. Nakayama, K. Tatsumi, M. Maeda, S. Imai, S. Umesako, H. Yamamoto, J. Hilgers and N. H. Sarkar, “Overexpression of the p53 Gene Product in Canine Mammary Tumors,” Oncology Reports, Vol. 8, No. 6, 2001, pp. 1215-1219.
[37] K. Ozaki, T. Yamagami, K. Nomura and I. Narama, “Mast Cell Tumors of the Gastrointestinal Tract in 39 Dogs,” Veterinary Pathology, Vol. 39, No. 5, 2002, pp. 557-564. doi:10.1354/vp.39-5-557
[38] A. Porrello, P. Cardelli and E. P. Spugnini, “Oncology of Companion Animals as a Model for Humans—An Overview of Tumor Histotypes,” Journal of Experimental & Clinical Cancer Research, Vol. 25, No. 1, 2006, pp. 97-105.
[39] K. L. Tsai, L. A. Clark and K. E. Murphy, “Understanding Hereditary Diseases Using the Dog and Human as Companion Model Systems,” Mammalian Genome, Vol. 18, No. 6-7, 2007, pp. 444-451. doi:10.1007/s00335-007-9037-1
[40] E. K. Karlsson and K. Lindblad-Toh, “Leader of the Pack: Gene Mapping in Dogs and Other Model Organisms,” Nature Reviews Genetics, Vol. 9, No. 9, 2008, pp. 713-725. doi:10.1038/nrg2382.
[41] E. A. Ostrander and E. Giniger, “Semper Fidelis: What Man’s Best Friend Can Teach Us about Human Biology and Disease,” The American Journal of Human Genetics, Vol. 61, No. 3, 1997, pp. 475-480. doi:10.1086/515522
[42] T. J. Jónasdóttir, C. S. Mellersh, L. Moe, et al., “Genetic Mapping of a Naturally Occurring Hereditary Renal Cancer Syndrome in Dogs,” Proceedings of the National Academy Sciences of the United States of America, Vol. 97, No. 8, 2000, pp. 4132-4137. doi:10.1073/pnas.070053397
[43] L. L. Hsiao, F. Dangond, T. Yoshida, R. Hong, R. V. Jensen, et al., “A Compendium of Gene Expression in Normal Human Tissues,” Physiol Genomics, Vol. 7, No. 2, 2001, pp. 97-104.
[44] A. Saito-Hisaminato, T. Katagiri, S. Kakiuchi, T. Nakamura, T. Tsunoda, et al., “Genome-Wide Profiling of Gene Expression in 29 Normal Human Tissues with a cDNA Microarray,” DNA Research, Vol. 9, No. 2, 2002, pp. 35-45. doi:10.1093/dnares/9.2.35
[45] R. Shyamsundar, Y. H. Kim, J. P. Higgins, K. Montgomery, M. Jorden, et al., “A DNA Microarray Survey of Gene Expression in Normal Human Tissues,” Genome Biology, Vol. 6, No. 3, 2005, p. R22. doi:10.1186/gb-2005-6-3-r22
[46] G. Son, S. Bilke, S. Davis, B. T. Greer, J. S. Wei, et al., “Database of mRNA Gene Expression Profiles of Multiple Human Organs,” Genome Research, Vol. 15, No. 3, 2005, pp. 443-450. doi:10.1101/gr.3124505
[47] J. Briggs, M. Paoloni, Q. R. Chen, X. Wen, J. Khan and C. Khanna, “A Compendium of Canine Normal Tissue Gene Expression,” PLoS One, Vol. 6, No. 5, 2011, pp. 101-107. doi:10.1371/journal.pone.0017107
[48] E. A. Ostrander, F. Galibert and D. F. Patterson, “Canine Genetics Comes of Age,” Trends in Genetics, Vol. 16, No. 3, 2000, pp. 117-123. doi:10.1016/S0168-9525(99)01958-7
[49] D. Patterson, “Companion Animal Medicine in the Age of Medical Genetics,” Journal of Veterinary Internal Medicine, Vol. 14, No. 1, 2000, pp. 1-9. doi:10.1111/j.1939-1676.2000.tb01492.x
[50] M. Breen, et al., “Chromosome-Specific Single-Locus FISH Probes Allow Anchorage of an 1800 Marker Integrated Radiation-Hybrid/Linkage Map of the Domestic Dog Genome to All Chromosomes,” Genome Research, Vol. 11, No. 10, 2001, pp. 1784-1795. doi:10.1101/gr.189401
[51] M. Breen, J. Bullerdiek and C. F. Langford, “The DAPI Banded Karyotype of the Domestic Dog (Canis Familiaris) Generated Using Chromosome-Specific Paint Probes,” Chromosome Research, Vol. 7, No. 5, 1999, pp. 401-406. doi:10.1023/A:1009224232134
[52] M. Breen, et al., “An Integrated 4249 Marker FISH/RH Map of the Canine Genome,” BMC Genomics, Vol. 5, 2004, p. 65. doi:10.1186/1471-2164-5-65
[53] C. Hitte, et al., “Facilitating Genome Navigation: Survey Sequencing and Dense Radiation-Hybrid Gene Mapping,” Nature Reviews Genetics, Vol. 6, No. 8, 2005, pp. 643-648. doi:10.1038/nrg1658
[54] R. Li, et al., “Construction and Characterization of an Eightfold Redundant Dog Genomic Bacterial Artificial Chromosome Library,” Genomics, Vol. 58, No. 1, 1999, pp. 9-17. doi:10.1006/geno.1999.5772
[55] E. F. Kirkness, et al., “The Dog Genome: Survey Sequencing and Comparative Analysis,” Science, Vol. 301, No. 5641, 2003, pp. 1898-1903. doi:10.1126/science.1086432
[56] N. Sutter and E. Ostrander, “Dog Star Rising: The Canine Genetic System,” Nature Reviews Genetics, Vol. 5, No. 12, 2004, pp. 900-910. doi:10.1038/nrg1492
[57] F. Galibert, C. Andre and C. Hitte, “Dog as a Mammalian Genetic Model [in French],” Medicine Science (Paris), Vol. 20, No. 8-9, 2004, pp.761-766.
[58] R. Klopfleisch, D. Lenze, M. Hummel and A. D. Gruber, “Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile That Partly Overlaps with Human Breast Cancer Profiles,” BMC Caner, Vol. 10, 2010, p. 618. doi:10.1186/1471-2407-10-618
[59] A. Nieto, M. D. Perez-Alenza, N. Del Castillo, E. Tabanera, M. Castano and L. Pena, “BRCA1 Expression in Canine Mammary Dysplasias and Tumours: Relationship with Prognostic Variables,” Journal of Comparative Pathology, Vol. 128, No. 4, 2003, pp. 260-268. doi:10.1053/jcpa.2002.0631
[60] S. K. Muthuswamy, D. Li, S. Lelievre, M. J. Bissell and J. S. Brugge, “ErbB2, But Not ErbB1, Reinitiates Proliferation and Induces Luminal Repopulation in Epithelial Acini,” Nature Cell Biology, Vol. 3, No. 9, 2001, pp. 785-792. doi:10.1038/ncb0901-785
[61] E. S. Lander and N. J. Schork, “Genetic Dissection of Complex Traits,” Science, Vol. 265, No. 5181, 1994, pp. 2037-2048. doi:10.1126/science.8091226
[62] X. Lu, Z. C. Wang, J. D. Iglehart, X. Zhang and A. L. Richardson, “Predicting Features of Breast Cancer with Gene Expression Patterns,” Breast Cancer Research and Treatment, Vol. 108, No. 2, 2008, pp. 191-201. doi:10.1007/s10549-007-9596-6
[63] B. Weigelt, Z. Hu, X. He, C. Livasy, L. A. Carey, M. G. Ewend, A. M. Glas, C. M. Perou and L. J. Van’t Veer, “Molecular Portraits and 70-Gene Prognosis Signature Are Preserved throughout the Metastatic Process of Breast Cancer,” Cancer Research, Vol. 65, No. 20, 2005, pp. 9155-9158. doi:10.1158/0008-5472.CAN-05-2553
[64] L. J. Van‘t Veer, H. Dai, M. J. Van de Vijver, Y. D. He, A. A. Hart, M. Mao, H. L. Peterse, K. Van der Kooy, M. J. Marton, A. T. Witteveen, et al., “Gene Expression Profiling Predicts Clinical Outcome of Breast Cancer,” Nature, Vol. 415, No. 6871, 2002, pp. 530-536. doi:10.1038/415530a
[65] P. Uva, L. Aurisicchio, J. Watters, A. Loboda, A. Kulkarni, J. Castle, F. Palombo, V. Viti, G. Mesiti, V. Zappulli, et al., “Comparative Expression Pathway Analysis of Human and Canine Mammary Tumors,” BMC Genomics, Vol. 10, No. 135, 2009, p. 135. doi:10.1186/1471-2164-10-135
[66] K. Strauch, et al., “How to Model a Complex Trait. General Considerations and Suggestions,” Human Heredity, Vol. 55, No. 4, 2003, pp. 202-210. doi:10.1159/000073204
[67] E. K. Karlsson and K. Lindblad-Toh, “Leader of the Pack: Gene Mapping in Dogs and Other Model Organisms,” Nature Reviews Genetics, Vol. 9, No. 9, 2008, pp. 713-725. doi:10.1038/nrg2382
[68] T. A. Manolio, et al., “Finding the Missing Heritability of Complex Diseases,” Nature, Vol. 461, No. 7265, 2009, pp. 747-753. doi:10.1038/nature08494
[69] M. Paoloni and C. Khanna, “Translation of New Cancer Treatments from Pet Dogs to Humans,” Nature Reviews Genetics, Vol. 8, No. 2, 2008, pp. 147-156. doi:10.1038/nrc2273
[70] H. G. Parker, A. L. Shearin and E. A. Ostrander, “Man’s Best Friend Becomes Biology’s Best in Show: Genome Analyses in the Domestic Dog,” Annual Reviews of Genetics, Vol. 44, 2010, pp. 309-336. doi:10.1146/annurev-genet-102808-115200

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.