“Targeting” renal cell carcinoma patients with “targeted” agents: Are we there yet?

Abstract

The rapid approval of several novel agents, targeting the vascular endothelial growth factor or mammalian target of rapamycin pathways (sunitinib, pazopanib, sorafenib, axitinib, bevacizumab, everolimus, temsirolimus) has given to metastatic renal cell carcinoma (mRCC) patients and their treating physicians many new and effective therapeutic options. The treatment paradigm for these patients is rapidly evolving, with future studies needed to define the optimal sequencing of these new agents. Despite progresses, no validated biomarkers able to predict clinical outcome or useful to guide patient selection for treatment are currently available. Recent studies have suggested that some biomarkers, including cytokines, circulating proangiogenic factors, markers of hypoxia or targets of signaling pathways are potentially promising prognostic or predictive factors in mRCC. We present an overview of the most recent developments in identifying biomarkers for targeted therapies in advanced RCC.

Keywords: Biomarkers; Renal cell carcinoma; Prognostic biomarker; Predictive biomarker; Vascular endothelial growth factor tyrosine kinase inhibitors; Mammalian target of rapamycin inhibitors

Core tip: To date, there are no fully validated biomarkers for daily clinical use in renal cell carcinoma (RCC) treatment and the therapeutic decisions still depend exclusively on morphological and clinical criteria. Predictive markers of response are not yet available and consequently, all patients continue to be exposed to potentially toxic therapies without certainty of clinical benefit. The identification of reliable biomarkers could represent the turning point of the personalized treatment in RCC. Therefore, the design of clinical trials based on a biomarkers-approach is highly desirable in order to minimize costs and risks of treatments and to maximize the benefit to the patient.