Journal of Veterinary Clinics (한국임상수의학회지)

The Korean Society of Veterinary Clinics (한국임상수의학회)
권호 표지
DOI QR코드

DOI QR Code

Tyrosine Kinase Inhibitor as Clinical Application Feasibility in Canine Intractable Tumor Diseases

  • Choi, Eul-Soo (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Song, Joong-Hyun (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Shin, Jong-Il (Department of Pathobiology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University) ;
  • Sur, Jung-Hyang (Department of Pathobiology, Small Animal Tumor Diagnostic Center, College of Veterinary Medicine, Konkuk University) ;
  • Kang, Byeong-Teck (Laboratory of Veterinary Dermatology and Neurology, College of Veterinary Medicine, Chungbuk National University) ;
  • An, Su-Jin (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Cho, Kyu-Woan (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Jung, Dong-In (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University)
  • Received : 2016.07.08
  • Accepted : 2016.08.16
  • Published : 2016.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions. This study aims to show that the actions of growth factors associated with PDGFR-${\alpha}$, PDGFR-${\beta}$, VEGFR-2, c-KIT, and c-ABL, which are used in veterinary medicine, are expressed in canine intractable tumors. This study used archival cases of canine paraganglioma, gastrointestinal adenocarcinoma, hepatocellular carcinoma, and renal cell carcinoma. Tissues had been immunohistochemical analysis. The antibodies used were PDGFR-${\alpha}$, PDGFR-${\beta}$, c-kit, VEGFR-2, and c-Abl. PDGFR-${\alpha}$ was expressed only in HCC, and PDGFR-${\beta}$ was expressed in all tumors. VEGFR was also only expressed in HCC, and c-KIT has been expressed in HCC, paraganglioma, and small intestinal adenocarcinoma. c-Abl was expressed in all cancers, but was weakly expressed in paraganglioma, while more than moderately expressed in other tissues. In conclusion, this study investigated how TKIs used in human medicine can be applied to canine intractable tumors, through immunohistochemistry. The results indicate that there may be an application for TKIs in treating canine intractable tumors.

Keywords

References

  1. Ayala-Ramirez M, Chougnet CN, Habra MA, Palmer JL, Leboulleux S, Cabanillas ME, Caramella C, Anderson P, Al Ghuzlan A, Waguespack SG. Treatment with sunitinib for patients with progressive metastatic pheochromocytomas and sympathetic paragangliomas. J Clin Endocrinol Metab 2012; 97: 4040-4050. https://doi.org/10.1210/jc.2012-2356
  2. Cassol CA, Winer D, Liu W, Guo M, Ezzat S, Asa SL. Tyrosine kinase receptors as molecular targets in pheochromocytomas and paragangliomas. Mod Pathol 2014; 27: 1050-1062. https://doi.org/10.1038/modpathol.2013.233
  3. Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005; 353: 2477-2490. https://doi.org/10.1056/NEJMra043172
  4. Cosgrove SB, Wren JA, Cleaver DM, Martin DD, Walsh KF, Harfst JA, Follis SL, King VL, Boucher JF, Stegemann MR. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol 2013; 24: 479-e114. https://doi.org/10.1111/vde.12047
  5. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008; 8: 579-591. https://doi.org/10.1038/nrc2403
  6. Escudier B, Albiges L, Sonpavde G. Optimal management of metastatic renal cell carcinoma: current status. Drugs 2013; 73: 427-438. https://doi.org/10.1007/s40265-013-0043-1
  7. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature 2005; 438: 967-974. https://doi.org/10.1038/nature04483
  8. Gil da Costa RM, Oliveira JP, Saraiva AL, Seixas F, Faria F, Gartner F, Pires MA, Lopes C. Immunohistochemical characterization of 13 canine renal cell carcinomas. Vet Pathol 2011; 48: 427-432. https://doi.org/10.1177/0300985810381909
  9. Hahn K, Oglivie G, Rusk T, Devauchelle P, Leblanc A, Legendre A, Powers B, Leventhal P, Kinet J, Palmerini F. Masitinib is safe and effective for the treatment of canine mast cell tumors. J Vet Intern Med 2008; 22: 1301-1309. https://doi.org/10.1111/j.1939-1676.2008.0190.x
  10. Hahn KA, Legendre AM, Shaw NG, Phillips B, Ogilvie GK, Prescott DM, Atwater SW, Carreras JK, Lana SE, Ladue T. Evaluation of 12-and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors. Am J Vet Res 2010; 71: 1354-1361. https://doi.org/10.2460/ajvr.71.11.1354
  11. Heldin C. Targeting the PDGF signaling pathway in tumor treatment. J Cell Commun Signal 2013; 11: 97. https://doi.org/10.1186/1478-811X-11-97
  12. Heldin C, Eriksson U, Ostman A. New members of the platelet-derived growth factor family of mitogens. Arch Biochem Biophys 2002; 398: 284-290. https://doi.org/10.1006/abbi.2001.2707
  13. Jain RK. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer cell 2014; 26: 605-622. https://doi.org/10.1016/j.ccell.2014.10.006
  14. Jung HW, Lee HC, Kim JH, Jang HM, Moon JH, Sur JH, Ha J, Jung DI. Imatinib mesylate plus hydroxyurea chemotherapy for cerebellar meningioma in a Belgian Malinois dog. J Vet Med Sci 2014; 76: 1545-1548. https://doi.org/10.1292/jvms.14-0001
  15. Jyung RW, LeClair EE, Bernat RA, Kang TS, Ung F, McKenna MJ, Tuan RS. Expression of angiogenic growth factors in paragangliomas. Laryngoscope 2000; 110: 161-167. https://doi.org/10.1097/00005537-200001000-00029
  16. Katayama R, Huelsmeyer MK, Marr AK, Kurzman ID, Thamm DH, Vail DM. Imatinib mesylate inhibits platelet-derived growth factor activity and increases chemosensitivity in feline vaccine-associated sarcoma. Cancer Chemother Pharmacol 2004; 54: 25-33. https://doi.org/10.1007/s00280-004-0780-7
  17. Lachowicz JL, Post GS, Brodsky E. A Phase I Clinical Trial Evaluating Imatinib Mesylate (Gleevec) in Tumor-Bearing Cats. J Vet Intern Med 2005; 19: 860-864. https://doi.org/10.1111/j.1939-1676.2005.tb02778.x
  18. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991; 64: 327-336. https://doi.org/10.1016/0092-8674(91)90642-C
  19. Liovet J, Ricci S, Mazzaferro V. Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): Results of a Phase III randomized placebo-controlled trial (SHARP trial). 2007 ASCO Annual Meeting Proceedings Part I. J Clin Onc 2007; 25.
  20. London CA. Tyrosine kinase inhibitors in veterinary medicine. Top Companion Anim Med 2009; 24: 106-112. https://doi.org/10.1053/j.tcam.2009.02.002
  21. London CA, Hannah AL, Zadovoskaya R, Chien MB, Kollias-Baker C, Rosenberg M, Downing S, Post G, Boucher J, Shenoy N, Mendel DB, McMahon G, Cherrington JM. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res 2003; 9: 2755-2768.
  22. London CA, Malpas PB, Wood-Follis SL, Boucher JF, Rusk AW, Rosenberg MP, Henry CJ, Mitchener KL, Klein MK, Hintermeister JG, Bergman PJ, Couto GC, Mauldin GN, Michels GM. Multi-center, placebo-controlled, double-blind, randomized study of oral toceranib phosphate (SU11654), a receptor tyrosine kinase inhibitor, for the treatment of dogs with recurrent (either local or distant) mast cell tumor following surgical excision. Clin Cancer Res 2009; 15: 3856-3865. https://doi.org/10.1158/1078-0432.CCR-08-1860
  23. Maniscalco L, Iussich S, Morello E, Martano M, Biolatti B, Riondato F, Della Salda L, Romanucci M, Malatesta D, Bongiovanni L. PDGFs and PDGFRs in canine osteosarcoma: new targets for innovative therapeutic strategies in comparative oncology. Vet J 2013; 195: 41-47. https://doi.org/10.1016/j.tvjl.2012.05.003
  24. Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121-128. https://doi.org/10.1016/S1470-2045(09)70364-X
  25. Motzer RJ. Renal cell carcinoma: a priority malignancy for development and study of novel therapies. J Clin Oncol 2003; 21: 1193-1194. https://doi.org/10.1200/JCO.2003.12.072
  26. Ostman A. PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev 2004; 15: 275-286. https://doi.org/10.1016/j.cytogfr.2004.03.002
  27. Paradis V, Lagha NB, Zeimoura L, Blanchet P, Eschwege P, Ba N, Benoit G, Jardin A, Bedossa P. Expression of vascular endothelial growth factor in renal cell carcinomas. Virchows Arch 2000; 436: 351-356. https://doi.org/10.1007/s004280050458
  28. Park KS, Lee JL, Ahn H, Koh JM, Park I, Choi JS, Kim YR, Park TS, Ahn JH, Lee DH, Kim TW, Lee JS. Sunitinib, a novel therapy for anthracycline- and cisplatin-refractory malignant pheochromocytoma. Jpn J Clin Oncol 2009; 39: 327-331. https://doi.org/10.1093/jjco/hyp005
  29. Petit A, Castillo M, Santos M, Mellado B, Alcover JB, Mallofre C. KIT expression in chromophobe renal cell carcinoma: comparative immunohistochemical analysis of KIT expression in different renal cell neoplasms. Am J Surg Pathol 2004; 28: 676-678. https://doi.org/10.1097/00000478-200405000-00017
  30. Raica M, Cimpean AM, Anghel A. Immunohistochemical expression of vascular endothelial growth factor (VEGF) does not correlate with microvessel density in renal cell carcinoma. Neoplasma 2007; 54: 278-284.
  31. Rini BI, Small EJ. Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma. J Clin Oncol 2005; 23: 1028-1043. https://doi.org/10.1200/JCO.2005.01.186
  32. Rivet J, Mourah S, Murata H, Mounier N, Pisonero H, Mongiat-Artus P, Teillac P, Calvo F, Janin A, Dosquet C. VEGF and VEGFR-1 are coexpressed by epithelial and stromal cells of renal cell carcinoma. Cancer 2008; 112: 433-442. https://doi.org/10.1002/cncr.23186
  33. Staser K, Yang FC, Clapp DW. Mast cells and the neurofibroma microenvironment. Blood 2010; 116: 157-164. https://doi.org/10.1182/blood-2009-09-242875
  34. Staser K, Yang FC, Clapp DW. Pathogenesis of plexiform neurofibroma: tumor-stromal/hematopoietic interactions in tumor progression. Annu Rev Pathol 2012; 7: 469-495. https://doi.org/10.1146/annurev-pathol-011811-132441
  35. Stock P, Monga D, Tan X, Micsenyi A, Loizos N, Monga SP. Platelet-derived growth factor receptor-alpha: a novel therapeutic target in human hepatocellular cancer. Mol Cancer Ther 2007; 6: 1932-1941.
  36. Sulzbacher I, Traxler M, Mosberger I, Lang S, Chott A. Platelet-derived growth factor-AA and-${\alpha}$ receptor expression suggests an autocrine and/or paracrine loop in osteosarcoma. Mod Pathol 2000; 13: 632-637. https://doi.org/10.1038/modpathol.3880109
  37. Suzuki S, Dobashi Y, Hatakeyama Y, Tajiri R, Fujimura T, Heldin CH, Ooi A. Clinicopathological significance of platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-beta phosphorylation, and microvessel density in gastric cancer. BMC Cancer 2010; 10: 1471-2407-10-659.
  38. Uren A, Merchant M, Sun C, Vitolo M, Sun Y, Tsokos M, Illei P, Ladanyi M, Passaniti A, Mackall C. Beta-platelet-derived growth factor receptor mediates motility and growth of Ewing's sarcoma cells. Oncogene 2003; 22: 2334-2342. https://doi.org/10.1038/sj.onc.1206330
  39. Van Etten RA. Cycling, stressed-out and nervous: cellular functions of c-Abl. Trends Cell Biol 1999; 9: 179-186. https://doi.org/10.1016/S0962-8924(99)01549-4
  40. Veikkola T, Karkkainen M, Claesson-Welsh L, Alitalo K. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res 2000; 60: 203-212.