A molecular case report

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.

Keywords: :

• renal cell carcinoma
• molecular targeted therapy
• tyrosine kinase

Disclosure of Potential Conflicts of Interest

C.R. communicates potential conflicts of interest with regard to his role as consultant for Aveo, GSK, Bayer and Onyx and as a consultant and honoraria for Pfizer and Novartis. No potential conflicts of interest were disclosed by other authors.

Acknowledgments

We acknowledge the patient, and Dr. James Rheinwald of the Harvard Skin Diseases Research Center. We are also grateful to Dr. Toni Choueiri, Dr. Christopher Doyle, Dr. Michelle Hirsch and Dr. Jeanne Shen and the Brigham and Women’s Hospital. Aaron Wortham is a predoctoral fellow of the National Institutes of Health under award number T32CA106195. The OHSU Knight Cancer Institute is supported by P30 CA069533.