title: A molecular case report: functional assay of tyrosine kinase inhibitors in cells from a patient's primary renal cell carcinoma.
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.
authors.affiliation: Knight Cancer Institute and Department of Dermatology, Oregon Health and Science University, Portland, OR, USA. kuleszma@ohsu.edu and ryanc@ ohsu.edu
authors.forename: Molly F
authors.initials: MF
authors.lastname: Kulesz-Martin
authors.forename: James
authors.initials: J
authors.lastname: Lagowski
authors.forename: Susan
authors.initials: S
authors.lastname: Olson
authors.forename: Aaron
authors.initials: A
authors.lastname: Wortham
authors.forename: Toni
authors.initials: T
authors.lastname: West
authors.forename: George
authors.initials: G
authors.lastname: Thomas
authors.forename: Christopher
authors.initials: C
authors.lastname: Ryan
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Tyner
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000037:antagonists & inhibitors; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019061:src-Family Kinases