Brief Communication

A molecular case report: Functional assay of tyrosine kinase inhibitors in cells from a patient’s primary renal cell carcinoma

Volume 14, Issue 2   February 2013
Pages 95 - 99
http://dx.doi.org/10.4161/cbt.22960
Keywords: molecular targeted therapy, renal cell carcinoma, tyrosine kinase
Authors: Molly Kulesz-Martin, James Lagowski, Susan Olson, Aaron Wortham, Toni West, George Thomas, Christopher W. Ryan and Jeffrey W. Tyner

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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.

Received: November 9, 2012; Accepted: November 18, 2012; Published Online: November 28, 2012

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