Predictive molecular biomarkers to guide clinical decision making in kidney cancer: current progress and future challenges

Abstract

Although the past decade has seen a surfeit of new targeted therapies for renal cell carcinoma (RCC), no predictive molecular biomarker is currently used in routine clinical practice to guide personalized therapy as a companion diagnostic. Many putative biomarkers have been suggested, but none have undergone rigorous validation. There have been considerable advances in the biological understanding of RCC in recent years, with the development of accompanying molecular diagnostics that with additional validation, may be helpful for routine clinical decision making. In this review, we summarize the current understanding of predictive biomarkers in RCC management and also highlight upcoming developments of interest in biomarker research for personalizing RCC diagnostics and therapeutics.

Keywords:

• angiogenesis
• biomarker
• cytokine
• immunotherapy
• renal cell carcinoma

Financial & competing interests disclosure

M-H Tan and Y Choudhury have filed for patents for molecular diagnostics in renal cell carcinoma. M-H Tan has received research funding from Pfizer. This work is supported by the Institute of Bioengineering and Nanotechnology, Biomedical Research Council (Diagnostics Grant), and Agency for Science, Technology and Research, Singapore. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Renal cell carcinoma is a heterogeneous disease with unpredictable clinico-pathological behavior.

• Conventional treatment options with IL-2, anti-angiogenic agents or mTOR inhibitors are limited by efficacy and/or toxicity issues.

• In contemporary clinical practice, no predictive biomarker exists to rationally guide individual therapy.

• Several putative biomarkers have been shown to correlate with therapeutic efficacy, although none have been rigorously validated.

• Recently, clinically applicable PCR-based assays have identified a practical number of genes capable of risk-stratifying patients with renal cell carcinoma, and in addition, may predict their clinical benefit from tyrosine kinase inhibitors.

• These results encourage the development of simplified and convenient molecular diagnostic toolkits that may aid routine clinical decision making.

Notes