关键词: molecular targeted therapy renal cell carcinoma tyrosine kinase

Mesh : Antineoplastic Agents / pharmacology Carcinoma, Renal Cell / metabolism Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Humans Inhibitory Concentration 50 Kidney Neoplasms / metabolism Male Middle Aged Protein Kinase Inhibitors / pharmacology Von Hippel-Lindau Tumor Suppressor Protein / antagonists & inhibitors src-Family Kinases / antagonists & inhibitors

来  源:   DOI:10.4161/cbt.22960   PDF(Sci-hub)

Abstract:
Current therapies for Renal Cell Carcinoma favor vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase (TK) inhibitors (TKIs). In theory, these are most applicable in tumors that have lost VHL-with subsequent stabilization of HIF and upregulation of VEGF. A subset of patients harbor primary-refractory disease, as in this case, where there was no evidence for loss of VHL or chromosome 3p. We evaluated molecular targeted agents in viable tumor cells cultured from a patient\'s clear cell renal cell carcinoma (RCC). Of 66 agents, only dasatinib, an inhibitor of Src tyrosine kinase, strongly reduced viability of the patient\'s cultured kidney tumor cells. Immunostaining of the original primary tumor revealed strong positivity for VHL and Src protein expression. Functional evaluation of a patient\'s tumor cells appears feasible in the setting of RCC.
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