Delivering preventive, predictive and personalised cancer medicine for renal cell carcinoma: the challenge of tumour heterogeneity

Recent years have seen major advances in the management of metastatic renal cell carcinoma (mRCC). The tyrosine kinase and mammalian target of rapamycin inhibitors have resulted in disease control and improved survival for many patients with mRCC, but they have not led to preventive, predictive or personalised medicine (PPPM). Failure to achieve this rests ultimately with inadequate knowledge of tissue and molecular heterogeneity; discovery of these drugs was based upon identification of pathogenic molecular pathways in RCC, but research into molecular factors which underpin drug response, resistance and selection of therapy for individual patients has lagged well behind clinical trials of drug development. This review will provide an overview of the development of targeted drug therapies for mRCC, will discuss the challenges which currently impede the delivery of PPPM, including identification of biomarkers, drug resistance and molecular heterogeneity, and will propose research methodologies and technologies required to overcome these obstacles.