Targeted therapy of renal cell cancer.
Rapid development of treatment strategies for renal cell cancer (RCC) has occurred in recent years. Elucidation of the crucial role of the Von Hippel-Lindau (VHL) tumor suppressor gene in upregulating growth factors associated with angiogenesis has provided new insight into RCC biology and has identified specific targets for novel therapeutic strategies. For almost two decades, cytokine-based immunotherapy has remained a treatment of choice in advanced RCC patients. However, it has provided only modest improvement in clinical outcome and has been associated with severe toxicity. With the advent of novel therapies directly targeting the VEGF molecule or VEGF receptor signal transduction pathway, the clinical outcome in high-risk, advanced RCC has significantly improved. In phase III clinical trials, novel targeted agents - temsirolimus, sorafenib, sunitinib and bevacizumab - significantly prolonged progression-free survival of patients with metastatic RCC and, crucially, temsirolimus also prolonged overall survival in patients with high-risk disease. Despite the obvious clinical efficacy of novel targeted therapies in the treatment of RCC, many unanswered questions still remain; in particular, the efficacy of targeted agents in patients with low-risk RCC, the optimal sequence and combination of therapies for first-, second-, or third-line treatment, and the efficacy of this strategy in adjuvant settings.
University of Medical Sciences, GreatPoland Cancer Center, Department of Cancer Immunology, ul Garbary 15, 61-866 Poznan, Poland.pwysocki@plusnet.pl
Piotr J
PJ
Wysocki
Jakob
J
Zolnierek
Cezary
C
Szczylik
Andrzej
A
Mackiewicz
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016207:Cytokines / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011379:Prognosis
D000970:Antineoplastic Agents; D016207:Cytokines