Novel therapies for renal cell carcinoma

Metastatic renal cell cancer remains a disease which is difficult to treat medically. Prognosis often depends more on intrinsic disease features than on treatment choices. In this review, we examine novel therapies and scient ific directions surrounding the RCC treatment problem. Reports relating chr omosomal aberrations and of comparative gene expression analyses relating t o RCC, are reviewed briefly. The central role of the von Hippel Lindau prot ein in clear cell RCC pathogenesis is evident. The limited contribution of conventional cytotoxic chemotherapy is mentioned. Some clinically applied a gents whose clinical results are highlighted include 5-FU, retinoids, thali domide, razoxane and IL-12. Features of the pathophysiology of von Hippel L indau protein are described, with attention to potential novel therapies ta rgeting HIF-1 alpha, VEGF, TGF-beta1 and TGF-alpha pathways. Immunotherapy is being explored in many angles. Most basic are cytokine therapies incorpo rating new IL-2 and IFN-alpha schedules. Newer cytokine-based drugs include pegylated forms and IL-12. Allogeneic mini-transplantation has generated m uch interest. Tumour-associated antigens are being used to direct therapy u sing both identified and non-identified epitopes. A Variety of tumour-cell vaccine and dendritic-cell vaccine clinical approaches are discussed. Final ly, nephrectomy for known metastatic disease has been demonstrated to be he lpful in retrospective and now prospective trials. Resection of metastases is also discussed. We are optimistic that the further clinical development among these novel therapies will improve the outlook for metastatic RCC.