Effect of tyrosine kinase inhibition by imatinib mesylate on mast cell tumors in dogs.
BACKGROUND
Imatinib mesylate is a small molecule targeted at dysregulated protein-tyrosine kinase. Mutation of c-kit exon 11, which induces constitutive phosphorylation of KIT, is one of the mechanisms for the development or progression of mast cell tumor (MCT) in dogs. The purpose of this study was to examine the therapeutic potential of imatinib mesylate in canine MCT.


OBJECTIVE
Imatinib mesylate has activity against MCT in dogs, and response to treatment can be correlated to presence of mutation within exon 11 of c-kit.


METHODS
Twenty-one dogs with MCT with gross tumor burden and median tumor size of 7.2 cm (range, 1.0-25.3 cm) before treatment.


METHODS
Tumors were analyzed for mutation of c-kit exon 11. Imatinib mesylate was administered PO to the dogs at a dose of 10 mg/kg daily for 1-9 weeks.


RESULTS
Ten of 21 dogs (48%) had some beneficial response to imatinib mesylate treatment within 14 days of treatment initiation. All 5 dogs with a demonstrable c-kit mutation in exon 11 responded to the drug (1 complete remission, 4 partial remission).


CONCLUSIONS
Imatinib mesylate has clinical activity against MCT in dogs. Response could not be predicted based on presence of absence of a mutation in exon 11 of c-kit.
Department of Veterinary Clinical Pathology, Nippon Veterinary and Life Science University, Tokyo, Japan.
M
M
Isotani
N
N
Ishida
M
M
Tominaga
K
K
Tamura
H
H
Yagihara
S
S
Ochi
R
R
Kato
T
T
Kobayashi
M
M
Fujita
Y
Y
Fujino
A
A
Setoguchi
K
K
Ono
T
T
Washizu
M
M
Bonkobara
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D001549:Benzamides; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D000068877:Imatinib Mesylate; D008297:Male; D012515:Mast-Cell Sarcoma / Q000188:drug therapy / Q000662:veterinary*; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases