Cancer and Metastasis Reviews

, Volume 9, Issue 2, pp 125–136 | Cite as

Spontaneous tumors in dogs and cats: Models for the study of cancer biology and treatment

  • E. Gregory MacEwen
Article

Abstract

Spontaneous tumors in dogs and cats are appropriate and valid model tumor systems available for testing cancer therapeutic agents or studying cancer biology. The pet population is a vastly underutilized resource of animals available for study. Dogs and cats develop spontaneous tumors with histopathologic and biologic behavior similar to tumors that occur in humans. The tumors with potential relevance for human cancer biology include osteosarcoma, mammary carcinoma, oral melanoma, oral squamous cell carcinoma, nasal tumors, lung carcinoma, soft tissue sarcomas, and malignant non-Hodgkin's lymphoma.

Canine osteosarcoma is a malignant aggressive bone tumor with a 90% matastasis rate after surgical amputation. Its predictable metastatic rate and pattern and its relative resistance to chemotherapy make this tumor particularly attractive for studying anti-metastasis approaches. Canine and feline malignant mammary tumors are fairly common in middle-aged animals and have a metastatic pattern similar to that in women; that is, primarily to regional lymph nodes and lungs. Chemotherapy has been minimally effective, and these tumors may be better models for testing biological response modifiers.

Oral tumors, especially melanomas, are the most common canine malignant tumor in the oral cavity. Metastasis is frequent, and the response to chemotherapy and radiation has been disappointing. This tumor can be treated with anti-metastatic approaches or biological response modifiers. Squamous cell carcinomas, especially in the gum, are excellent models for radiation therapy studies.

Nasal carcinomas are commonly treated with radiation therapy. They tend to metastasize slowly, but have a high local recurrence rate. This tumor is suitable for studying radiation therapy approaches.

Primary lung tumors and soft tissue sarcomas are excellent models for studying combined modality therapy such as surgery with chemotherapy or biological response modifiers.

Finally, non-Hodgkin's lymphoma is a common neoplastic process seen in the dog. These tumors respond to combination chemotherapy and have great potential as a model for newer chemotherapeutic agents and biological response modifiers.

This paper will further elaborate on the relative merits of each tumor type as a model for human cancer therapy and biology.

Key words

spontaneous tumors dogs and cats animal models metastasis radiation biological response modifiers chemotherapy 

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References

  1. 1.
    Hewitt HB: The choice of animal tumors for experimental studies of cancer therapy. Adv in Cancer Res 27: 149–200, 1978Google Scholar
  2. 2.
    Herberman RB: Counterpoint: Animal tumor models and their relevance to human tumor immunology. J Biol Resp Modif 2: 39–46, 1983Google Scholar
  3. 3.
    Hewitt HB: Second point: Animal tumor models and their relevance to human tumor immunology. J Biol Resp Modif 2: 210–216, 1983Google Scholar
  4. 4.
    Herberman RB: Second counterpoint: Animal tumor models and their relevance to human tumor immunology. J Biol Resp Modif 2: 217–226, 1983Google Scholar
  5. 5.
    Bronson RT: Variation in age at death of dogs of different sexes and breeds. Am J Vet Res 43: 2057–2059, 1982Google Scholar
  6. 6.
    Priester WA (ed): The occurrence of tumors in domestic animals. NCI Momogr No. 54, Nov. 1980Google Scholar
  7. 7.
    Misdorp W, Hart AAM: Some prognostic and epidemiologic factors in canine osteosarcoma. J Natl Cancer Inst 62: 537–545, 1979Google Scholar
  8. 8.
    Brodey RS, Riser WH: Canine osteosarcoma: A clinicopathologic study of 194 cases. Clin Orthop 62: 54–64, 1969Google Scholar
  9. 9.
    Brodey RS: Surgical treatment of canine osteosarcoma. J Am Vet Med Assoc 147: 729–735, 1965Google Scholar
  10. 10.
    Madewell BR, Leighton RC, Theilen AG: Amputation and doxorubicin for treatment of canine and feline osteogenic sarcoma. Eur J Cancer 4: 287–293, 1978Google Scholar
  11. 11.
    Cotter SM, Parker LM: High dose methotrexate and leucovorin rescure in dogs with osteogenic sarcoma. Am J Vet Res 39: 1943–1945, 1978Google Scholar
  12. 12.
    Henness AM, Theilen GH, Park RD, Buhles WC: Combination therapy for canine osteosarcoma. J Am Vet Med Assoc 179: 1076–1081, 1977Google Scholar
  13. 13.
    Mauldin GN, Matus RE, Withrow SJ, Patnaik AK: Canine osteosarcoma treatment by amputation versus amputation and adjuvant chemotherapy using doxorubicin and cisplatin. J Vet Int Med 2: 177–180, 1988Google Scholar
  14. 14.
    Shapiro W, Fossum TW, Kitchell BW, Couto CG, Theilen GH: Use of cisplatin for the treatment of appendicular osteosarcoma in dogs. J Am Vet Med Assoc 4: 507–51, 1988Google Scholar
  15. 15.
    Straw RC, Withrow SJ, Richter SL, Powers BE, Klein MK, Postorino NC, LaRue SM, Ogilvie GK, Vail DM, McGee M, Dickson K: Amputation and cisplatin for treatment of canine osteosarcoma. J Am Vet Med Assoc (in press) 1990Google Scholar
  16. 16.
    Meyer JA, Dueland RT, MacEwen EG, Macy DW, Hoefle WD, Richardson RC, Alexander JW, Trotter E, Hause WR: Canine osteogenic sarcoma treated with amputation and MER. Adverse effects of splenectomy on survival. Cancer 49: 1613–1616, 1982Google Scholar
  17. 17.
    Weiden PL, Deeg HF, Graham TC, Storb R: Canine osteosarcoma failure of intravenous or intralesional BCG as adjuvant immunotherapy. Cancer Immunol Immunother 11: 69–72, 1981Google Scholar
  18. 18.
    MacEwen EG, Kurzman ID, Smith BW, Rosenthal RC, Manley PA, Roush JK, Howard PE. Therapy of osteosarcoma in dogs with intravenous injection of liposome-encapsulated MTP. J Natl Cancer Inst 81: 935–939, 1989Google Scholar
  19. 19.
    MacEwen EG, Kurzman ID, Rosenthal R, Fox L: Randomized study using adjuvant liposome-encapsulated MTP-PE with cisplatin in the canine osteosarcoma model — preliminary results. (Abstract) Combining Biological Response Modifiers with Cytotoxics in the Treatment of Cancer. Developing a Rational Approach to a New Therapy. Proceedings, March 5–17, 1990, Baltimore, MDGoogle Scholar
  20. 20.
    Schneider R, Dorn CR, Taylor DON: Factors influencing canine mammary cancer development and postsurgical survival. J Natl Cancer Inst 43: 1249–1261, 1969Google Scholar
  21. 21.
    MacEwen EG, Panko WB, Patnaik AK, Harvey HJ: Estrogen receptor in canine mammary tumors. Cancer Res 42: 2255–2259, 1982Google Scholar
  22. 22.
    Martin PM, Cortard M, Mialot JP: Animal models for hormone-dependent human breast cancer.Cancer Chemotherapy Pharmacol 2: 13–17, 1984Google Scholar
  23. 23.
    Gilbertson SR, Kurzman ID, Zachrau RE, Hurvitz AI: Canine mammary epithelial neoplasms: Biological implications of morphologic characteristics assessed in 232 dogs. Vet Path 20: 127–142, 1983Google Scholar
  24. 24.
    Kurzman ID, Gilbertson SR: Prognostic factors in canine mammary tumors. Semin Vet Med Surg 1: 25–32, 1986Google Scholar
  25. 25.
    Misdorp W, Hart AMM: Canine mammary cancer. I Prognosis. J Small Anim Pract 20: 285–294, 1979Google Scholar
  26. 26.
    MacEwen EG, Harvey HJ, Patnaik AK, Mooney S, Hayes AA, Hardy WD: Evaluation of effects of levamisole and surgery on canine mammary cancer. J Biol Resp Modif 4: 418–426, 1985Google Scholar
  27. 27.
    Parodi AL, Misdorp W, Mialot JP: Intratumoral BCG and Corynebacterium parvum, therapy of canine mammary before radical mastectomy. Eur J Cancer 15: 172–177, 1983Google Scholar
  28. 28.
    Winters WP, Harris SC: Increased survival and interferon induction by BCG-CW immunotherapy in pet dogs with malignant mammary tumors. Abstract No. 964, p 244. Am Assoc Cancer Res, 1982Google Scholar
  29. 29.
    Sedlacek HH, Hagmeyer G, Seiler FR: Tumor therapy of neoplastic diseases with tumor cells and neuraminidases. Cancer Immunol Immunother 23: 192–199, 1986Google Scholar
  30. 30.
    Fowler EH, Wilson GP, Koestner AA: Biologic behavior of canine mammary neoplasms based on a histogenetic classification. Vet Pathol 11: 212–229, 1974Google Scholar
  31. 31.
    Elling H, Ungemach FR: Progesterone receptors in feline mammary cancer cytosol. J Cancer Res Clin Oncol 100: 325–327, 1981Google Scholar
  32. 32.
    MacEwen EG, Hayes AA, Harvey HJ, Patnaik AK, Mooney S, Passe S: Prognostic factors for feline mammary tumors. J Am Vet Med Assoc 185: 201–204, 1984Google Scholar
  33. 33.
    Weijer K, Hart AAM: Prognostic factors in feline mammary carcinoma. J Natl Cancer Inst 70: 709–710, 1983Google Scholar
  34. 34.
    Jeglum KA, DeGuzman E, Young K: Chemotherapy of advanced mammary adenocarcinoma in 14 cats. J Am Vet Med Assoc 187: 157–160, 1985Google Scholar
  35. 35.
    MacEwen EG, Hayes AA, Mooney S, Patnaik AK, Harvey HJ, Passe S, Hardy WD: Evaluation of effect of levamisole on feline mammary cancer. J Biol Resp Modif 5: 541–546, 1984Google Scholar
  36. 36.
    Jeglum KA, Hanna MG, Hoover HC, et al.: A prospectively randomized trial of adjuvant active specific immunotherapy in feline breast cancer. Am J Vet Res. (in press)Google Scholar
  37. 37.
    MacEwen EG, Patnaik AK, Harvey HJ, Hayes AA, Matus R: Canine oral melanoma: Comparison of surgery versus surgery plus Corynebacterium parvum. Cancer Invest 4: 397–402, 1986Google Scholar
  38. 38.
    Harvey HJ, MacEwen EG, Braun D, Patnaik AK, Withrow SJ: Prognostic criteria for dogs with oral melanoma. J Am Vet Assoc 178: 580–582, 1981Google Scholar
  39. 39.
    Gillette EL: Sponteneous canine neoplasms as models for therapeutic agents. Design of Models for Testing Cancer Therapeutic Agents. (IJ Fidler and RJ White eds) Van Nostrand Reinhold Co., New York, p. 185–192, 1982Google Scholar
  40. 40.
    Withrow SJ: Tumors of the respiratory system. Clinical Veterinary Oncology. (SJ Withrow, EG MacEwen eds) JB Lippincott Co., Philadelphia, PA, p. 215–233, 1989Google Scholar
  41. 41.
    Adams WM, Withrow SJ, Walshaw R, Turrell JM, Evans SM, Walker MA, Kurzman ID: Radiotherapy of malignant nasal tumors of 67 dogs. J Am Vet Med Assoc 191: 311–315, 1987Google Scholar
  42. 42.
    Thrall DE, Harvey CE: Radiotherapy of malignant nasal tumors in 21 dogs. J Am Vet Med Assoc 183: 663–666, 1983Google Scholar
  43. 43.
    Moulton JE, Von Tscharner C, Schneider R: Classification of lung carcinomas in the dog and cat. Vet Pathol 18: 513–528, 1981Google Scholar
  44. 44.
    Ogilvie GK, Haschek WM, Withrow SJ, Richardson RC, Harvey HJ, Henderson RA, Fowler JD, Norris AM, Tomlinson J, McCaw D, Klausner JS, Reschke RW, McKiernan BC: Classification of primary lung tumors in dogs: 210 cases (1975–1985). J Am Vet Med Assoc 195: 106–112, 1989Google Scholar
  45. 45.
    Oksanem A: Hemangiosarcoma in dogs. J Comp Pathol 88: 585–595, 1978Google Scholar
  46. 46.
    Brown NO, Patnaik AK, MacEwen EG: Canine hemangiosarcoma: Retrospective analysis of 104 cases. J Am Vet Med Assoc 186: 56–58, 1985Google Scholar
  47. 47.
    Greenelee PG, Filippa DA, Quimby FW, Patnaik AK, Calvano SE, Matus RE, Kimel M, Hurvitz AI, Lieberman PH: Lymphomas in dogs: A morphologic, immunologic, and clinical study. Cancer, 1990 (in press)Google Scholar
  48. 48.
    MacEwen EG, Hayes AA, Matus RE, Kurzman ID: some prognostic factors for advanced multicentric lymphosarcoma in the dog. J Am Vet Med Assoc 190: 564–568, 1987Google Scholar
  49. 49.
    Fisher RI, Hubbard SM, DeVita VT: Facotrs predicting long-term survival in diffuse mixed, histocytic, or undifferential lymphoma. Blood 58: 45–51, 1981Google Scholar
  50. 50.
    MacEwen EG, Hayes AA, Mooney S, Patnaik AK, Kurzman ID: Levamisole as adjuvant to chemotherapy for canine lymphosarcoma. J Biol Resp Modif 4: 427–433, 1985Google Scholar
  51. 51.
    Jeglum KA, Young KA, Barnsley K, Whereat BA: Chemotherapy versus chemotherapy with intralymphatic tumor cell vaccine in canine lymphoma. Cancer 61: 2042–2050, 1988Google Scholar
  52. 52.
    Appelbaum FR, Deeg HJ, Storb R: Marrow transplant studies in dogs with malignant lymphoma. Transplantation 39: 499–504, 1985Google Scholar
  53. 53.
    MacEwen EG, Rosenthal R, Matus RE, Viau AT, Abuckowski A: An evaluation of asparaginase: polyethylene glycol conjugate against canine lymphosarcoma. Cancer 59: 2011–2015, 1987Google Scholar
  54. 54.
    Teske E, Rutteman GR, Van Heerde P, Misdorp W: L-asparaginase vs PEG L-asparaginase in non-Hodgkin's lymphosarcoma: a phase III clinical trial in a canine model. (abstr) Anticancer Res 8: 1117, 1988Google Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • E. Gregory MacEwen
    • 1
  1. 1.Department of Medical Sciences, Associate Dean for Clinical Affairs, School of Veterinary MedicineUniversity of WisconsinMadisonUSA

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