Target Molecule Expression Profiles in Metastatic Renal Cell Carcinoma: Development of Individual Targeted Therapy

ABSTRACT

The aim of this study is to analyze the level of target molecule expression in metastatic renal cell carcinoma (RCC) to determine whether there is a correlation between molecular marker expression and clinical response. Ten patients with metastatic RCC, who received receptor tyrosine kinase (RTK) targeted therapy after cytoreductive or radical nephrectomy, were included. The expression of target molecules relating to the RTK, mammalian target of rapamycin, hypoxia inducible factor, mitogen activated protein kinase, and adenosine monophosphate-activated protein kinase pathways were analyzed using real-time polymerase chain reaction and immunohistochemistry. We correlated the level of target molecule expression with clinical response, including efficacy and adverse events experience during RTK targeted therapy. All patients showed similar histological subtype and grade on pathological examination; however, the expression of RCC target molecules was very different among the patients. The expression of molecules related to the RTK pathway in RCC tissue as well as relative expression of molecules in RCC tissue compared to normal kidney tissue, were higher in patients who showed a good response to RTK targeted therapy compared to those that showed a poor response. Target molecule expression in normal kidney tissue was higher in patients who experienced high-grade adverse events than in patients who experienced low-grade events. Target molecule expression in metastatic RCC correlates with targeted therapy clinical response including efficacy and adverse events. Personalized target molecule expression profiles could be used to predict clinical response to different targeted therapies, thus helping optimization of targeted therapies for patients with metastatic RCC.