Successful response to imatinib in two dogs with inoperable grade III infiltrating mast cell tumours: a case report J.H., Kim H.J., Kim D.H., Yim J.H., Lee S.J., Park K.H., Yoon H.Y. (2016): Successful response to imatinib in two dogs with inoperable grade III infiltrating mast cell tumours: a case report. Veterinarni Medicina, 61: 467-473.
download PDF

Two dogs were presented owing to sudden rapid growth of cutaneous masses greater than 10 cm on the neck and axillary region, respectively. Based on history and results of physical examinations, blood work, fine needle aspiration, histopathological examination, and computed tomography, inoperable grade III infiltrating mast cell tumours were diagnosed. After the initiation of imatinib treatment, the masses markedly shrank and became undetectable within 10 days in both dogs, although none of the tumour specimens showed evidence of mutations in sequencing of c-kit exons 8 and 11. These results suggest that imatinib could be a therapeutic option in patients with surgically inoperable canine mast cell tumours, even those that are histopathologically high grade without c-kit exon 8 or 11 mutations.

Antonescu C. R. (2005): Acquired Resistance to Imatinib in Gastrointestinal Stromal Tumor Occurs Through Secondary Gene Mutation. Clinical Cancer Research, 11, 4182-4190
Bonkobara Makoto (2015): Dysregulation of tyrosine kinases and use of imatinib in small animal practice. The Veterinary Journal, 205, 180-188
Buchdunger Elisabeth, O'Reilley Terence, Wood Jeanette (2002): Pharmacology of imatinib (STI571). European Journal of Cancer, 38, S28-S36
Cooper Maureen, Tsai XinRu, Bennett Peter (2009): Combination CCNU and vinblastine chemotherapy for canine mast cell tumours: 57 cases. Veterinary and Comparative Oncology, 7, 196-206
Downing Sue, Chien May B., Kass Philip H., Moore Peter F., London Cheryl A. (2002): Prevalence and importance of internal tandem duplications in exons 11 and 12 of c- kit in mast cell tumors of dogs. American Journal of Veterinary Research, 63, 1718-1723
Druker Brian J., Lydon Nicholas B. (2000): Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia. Journal of Clinical Investigation, 105, 3-7
Galli SJ, Kitamura Y (1987): Genetically mast-cell-deficient W/Wv and Sl/Sld mice. Their value for the analysis of the roles of mast cells in biologic responses in vivo. The American Journal of Pathology 127, 191–198.
Galli SJ, Zsebo KM, Geissler EN (1994): The kit ligand, stem cell factor. Advances in Immunology 55, 1–96.
Gregory-Bryson Emmalena, Bartlett Elizabeth, Kiupel Matti, Hayes Schantel, Yuzbasiyan-Gurkan Vilma (2010): Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11. BMC Cancer, 10, 559-
Hahn K.A., Oglivie G., Rusk T., Devauchelle P., Leblanc A., Legendre A., Powers B., Leventhal P.S., Kinet J.-P., Palmerini F., Dubreuil P., Moussy A., Hermine O. (2008): Masitinib is Safe and Effective for the Treatment of Canine Mast Cell Tumors. Journal of Veterinary Internal Medicine, 22, 1301-1309
Isotani M., Ishida N., Tominaga M., Tamura K., Yagihara H., Ochi S., Kato R., Kobayashi T., Fujita M., Fujino Y., Setoguchi A., Ono K., Washizu T., Bonkobara M. (2008): Effect of Tyrosine Kinase Inhibition by Imatinib Mesylate on Mast Cell Tumors in Dogs. Journal of Veterinary Internal Medicine, 22, 985-988
Kobayashi Masato, Sugisaki Osamu, Ishii Noriko, Yamada Osamu, Ito Keita, Kuroki Shiori, Sasaki Yu, Ono Kenichiro, Washizu Tsukimi, Bonkobara Makoto (2012): Canine intestinal mast cell tumor with c-kit exon 8 mutation responsive to imatinib therapy. The Veterinary Journal, 193, 264-267
Kobie Keiko, Kawabata Mariko, Hioki Kyoji, Tanaka Akane, Matsuda Hiroshi, Mori Takashi, Maruo Kohji (2007): The tyrosine kinase inhibitor imatinib [STI571] induces regression of xenografted canine mast cell tumors in SCID mice. Research in Veterinary Science, 82, 239-241
Liao A. T. (): Inhibition of constitutively active forms of mutant kit by multitargeted indolinone tyrosine kinase inhibitors. Blood, 100, 585-593
London Cheryl A, Seguin Bernard (2003): Mast cell tumors in the dog. Veterinary Clinics of North America: Small Animal Practice, 33, 473-489
London Cheryl A, Galli Stephen J, Yuuki Toshifumi, Hu Zhi-Qing, Helfand Stuart C, Geissler Edwin N (1999): Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit. Experimental Hematology, 27, 689-697
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 (2003): Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clinical Cancer Research 9, 2755–2768.
London C. A., Malpas P. B., Wood-Follis S. L., Boucher J. F., Rusk A. W., Rosenberg M. P., Henry C. J., Mitchener K. L., Klein M. K., Hintermeister J. G., Bergman P. J., Couto G. C., Mauldin G. N., Michels G. M. (): 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. Clinical Cancer Research, 15, 3856-3865
Ma Yongsheng, Longley B. Jack, Wang Xiaomei, Blount John L., Langley Keith, Caughey George H. (1999): Clustering of Activating Mutations in c-KIT's Juxtamembrane Coding Region in Canine Mast Cell Neoplasms. Journal of Investigative Dermatology, 112, 165-170
Nagata Hiroshi, Okada Tadashi, Worobec Alexandra S., Semere Tekli, Metcalfe Dean D. (1997): <i>c-ki</i><i>t</i> Mutation in a Population of Patients with Mastocytosis. International Archives of Allergy and Immunology, 113, 184-186
NAKANO Yuko, KOBAYASHI Tetsuya, OSHIMA Fukiko, FUKAZAWA Eri, YAMAGAMI Tetsushi, SHIRAISHI Yozo, TAKANOSU Masamine (2014): Imatinib Responsiveness in Canine Mast Cell Tumors Carrying Novel Mutations of c-KIT Exon 11. Journal of Veterinary Medical Science, 76, 545-548
Pryer NK, Lee LB, Zadovaskaya R, Yu X, Sukbuntherng J, Cherrington JM, London CA. (2003): Proof of target for SU11654 inhibition of KIT phosphorylation in canine mast cell tumors. Clinical Cancer Research 9, 5729–5734.
Webster Joshua D., Yuzbasiyan-Gurkan Vilma, Kaneene John B., Miller RoseAnn, Resau James H., Kiupel Matti (2006): The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors. Neoplasia, 8, 104-111
Yamada Osamu, Kobayashi Masato, Sugisaki Osamu, Ishii Noriko, Ito Keita, Kuroki Shiori, Sasaki Yu, Isotani Mayu, Ono Kenichiro, Washizu Tsukimi, Bonkobara Makoto (2011): Imatinib elicited a favorable response in a dog with a mast cell tumor carrying a c-kit c.1523A>T mutation via suppression of constitutive KIT activation. Veterinary Immunology and Immunopathology, 142, 101-106
Zavodovskaya Regina, Chien May B., London Cheryl A. (2004): Use of Kit Internal Tandem Duplications to Establish Mast Cell Tumor Clonality in 2 Dogs. Journal of Veterinary Internal Medicine, 18, 915-917
Zemke D., Yamini B., Yuzbasiyan-Gurkan V. (2002): Mutations in the Juxtamembrane Domain of c-KIT Are Associated with Higher Grade Mast Cell Tumors in Dogs. Veterinary Pathology, 39, 529-535
download PDF

© 2020 Czech Academy of Agricultural Sciences