The most important recent advances in oncology have been the identification and therapeutic targeting of specific molecular changes in tumour biology (eg, EGFR and ALK mutations in lung cancer and HER2 amplification in breast cancer). The fundamental change in renal-cell carcinoma is somatic von Hippel—Lindau gene silencing, which drives tumour angiogenesis through VEGF overexpression, evident in the clinical activity reported with VEGF-targeting therapy. Notably, VEGF acts mainly in the tumour stoma...