Biomarkers: the next therapeutic hurdle in metastatic renal cell carcinoma

Abstract

Despite recent advances, metastatic renal cell carcinoma remains largely an incurable disease. Vascular endothelial growth factor and mammalian target of rapamycin inhibitors have provided improvements in clinical outcomes. High-dose interleukin 2 remains an option for highly selected patients and is associated with durable remissions in a small minority of patients. The toxicity profiles of specific agents and patient characteristics and comorbidities and costs have an important role in the current choice of therapy. Major challenges encountered in developing molecular biomarkers to guide therapy are tumour heterogeneity and standardisation of tissue collection and analysis. Although biomarkers are in their infancy of development, they should be a priority in early preclinical and clinical development in order to guide rational tailored development of emerging agents.

Figure 1

Candidate molecular biomarkers for the therapy of advanced RCC with VEGF or mTOR inhibitors. Abbreviations: Bev=bevacizumab; CEC=circulating endothelial cells; FGF=fibroblast growth factor; HIF=hypoxia-inducible factor; IGFR=insulin-like growth factor receptor; IL-8=interleukin-8; MDSC=myeloid-derived suppressor cells; PDGF=platelet derived growth factor; PlGF=placental growth factor; VEGFR2=VEGF receptor 2; VHL=Von Hippel Lindau.

Figure 2

Design of phase II trial of neoadjuvant frontline everolimus preceding cytoreductive nephrectomy for metastatic RCC.