Mesh : Animals Bone Neoplasms / diagnostic imaging drug therapy veterinary Cell Line, Tumor Dasatinib Dog Diseases / diagnostic imaging drug therapy Dogs Osteosarcoma / diagnostic imaging drug therapy veterinary Protein Kinase Inhibitors / administration & dosage pharmacokinetics Pyrimidines / administration & dosage pharmacokinetics Radiography Thiazoles / administration & dosage pharmacokinetics Time Factors src-Family Kinases / antagonists & inhibitors

来  源:   DOI:10.1002/pbc.24512   PDF(Sci-hub)

Abstract:
BACKGROUND: Effective targeted therapies are needed in sarcomas, but the biological heterogeneity of these tumors has presented a challenge to clinical integration of small molecule inhibitors in sarcoma treatment. Here we outline a process to personalize therapy for sarcomas through a case study of a canine with spontaneous osteosarcoma.
METHODS: Rapid establishment of a primary tumor cell culture is described, followed by efficient functional characterization of the tumor that identified the Src inhibitor dasatinib as the most effective targeted therapy for this individual dog.
RESULTS: Adjuvant dasatinib was administered for a total of 26 weeks following treatment with chemotherapy. Pharmacokinetic studies confirm that a therapeutic serum concentration was achieved at a tolerable dose of 0.75 mg/kg/day. The canine patient remains without evidence of recurrent disease 24 months following initial diagnosis.
CONCLUSIONS: The approach described through this illustrative case study is broadly applicable and might be used for other solid tumors in canines as well as in humans.
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