Renal cell carcinoma (RCC) comprises a heterogeneous group of histologically and molecularly distinct tumour subtypes. Current targeted therapies have improved survival in patients with advanced disease but complete response occurs rarely, if at all. The genomic characterization of RCC is central to the development of novel targeted therapies. Large-scale studies employing multiple 'omics' platforms have led to the identification of key driver genes and commonly altered pathways. Specific molecular alterations and signatures that correlate with tumour phenotype and clinical outcome have been identified and can be harnessed for patient management and counselling. RCC seems to be a remarkably diverse malignancy with significant intratumour and intertumour genetic heterogeneity. The tumour microenvironment is increasingly recognized as a vital regulator of RCC tumour biology. Patient factors, including immune response and drug metabolism, vary widely, which can lead to widely divergent responses to drug therapy. Intratumour heterogeneity poses a significant challenge to the development of personalized therapies in RCC as a single biopsy might not accurately represent the clonal population ultimately responsible for aggressive biologic behaviour. On the other hand, the diversity of genomic alterations in RCC could also afford opportunities for targeting unique pathways based on analysis of an individual tumour's molecular composition.
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