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Renal Cell Carcinoma: From Molecular Biology to Targeted Therapies

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International Manual of Oncology Practice

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Abstract

The prognosis and treatment of patients with metastatic renal cell carcinoma have substantially improved over the past few years; indeed, a number of molecularly targeted agents, developed thanks to the translation into the clinic of a more thoroughful knowledge of the genetics and molecular biology of this neoplasm, have reached the clinic. The rapid addition of novel therapeutic options targeting the VHL-HIF-VEGF axis, as well as the mTOR pathway, has revolutionized the treatment algorithm for this once-orphan diesease. Here we review both the biology behind these therapeutical improvements, as well as the results of the main trials conducted to date.

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References

  1. Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr (1999) Rising incidence of renal cell cancer in the United States. JAMA 281:1628–1631

    Article  PubMed  CAS  Google Scholar 

  2. Pantuck AJ, Zisman A, Belldegrun AS (2001) The changing natural history of renal cell carcinoma. J Urol 166:1611–1623

    Article  PubMed  CAS  Google Scholar 

  3. Naito S, Koga H, Yokomizo A et al (2000) Molecular analysis of mechanisms regulating drug sensitivity and the development of new chemotherapy strategies for genitourinary carcinomas. World J Surg 24:1183–1186

    Article  PubMed  CAS  Google Scholar 

  4. Enquist E, Zambiano N, Zbar B et al (2000) Molecular mechanisms of immune dysfunction in renal cell carcinoma. In: Bukowski RM, Novick AC (eds) Renal cell carcinoma. Molecular biology, immunology and clinical management. Humana Press, Totowa

    Google Scholar 

  5. Porta C, Bonomi L, Lillaz B et al (2007) Renal cell carcinoma-induced immunosuppression: an immunophenotypic study of lymphocyte subpopulations and of circulating dendritic cells in patients at first diagnosis. Anticancer Res 27:165–173

    PubMed  CAS  Google Scholar 

  6. Porta C, Paglino C, Imarisio I, Bonomi L (2007) Cytokine-based immunotherapy for advanced kidney cancer: past results and future perspectives in the era of molecularly targeted agents. Sci World J 7:837–849

    Article  CAS  Google Scholar 

  7. Maher E, Kaelin WG (1997) von Hippel-Lindau disease. Medicine 76:381–391

    Article  PubMed  CAS  Google Scholar 

  8. Kim WY, Kaelin WG (2004) Role of VHL gene mutation in human cancer. J Clin Onc 22:4991–5004

    Article  CAS  Google Scholar 

  9. Beroukhim R, Brunet JP, Di Napoli A et al (2009) Patterns of gene expression and copy-number alterations in von-Hippel Lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res 69:4674–4681

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Gnarra JR, Lerman MI, Zbar B, Linehan WM (1995) Genetics of renal-cell carcinoma and evidence for a critical role for von Hippel-Lindau in renal tumorigenesis. Semin Oncol 22:3–8

    PubMed  CAS  Google Scholar 

  11. Gnarra JR, Tory K, Wang Y et al (1994) Mutations of the VHL tumor suppressor gene in renal carcinoma. Nat Genet 7:85–90

    Article  PubMed  CAS  Google Scholar 

  12. Shuin T, Kondo K, Torigoe S et al (1994) Frequent somatic mutations and loss of heterozigosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. Cancer Res 54:2852–2855

    PubMed  CAS  Google Scholar 

  13. Herman JG, Latif F, Weng Y et al (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci U S A 91:9700–9704

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Kondo K, Yao M, Yoshida M et al (2002) Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer 34:58–68

    Article  PubMed  CAS  Google Scholar 

  15. BrauschH HW, Jahning H et al (1997) Sporadic pheochromocytomas are rarely associated with germline mutations in the VHL tumor suppressor gene or the ret protooncogene. J Clin Endocrinol Metab 82:4101–4104

    Google Scholar 

  16. Clifford SC, Prowse AH, Affara NA et al (1998) Inactivation of the von Hippel-Lindau tumor suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma: evidence for a VHL-indipendent pathway in clear cell renal tumourigenesis. Genes Chromosomes Cancer 22:200–209

    Article  PubMed  CAS  Google Scholar 

  17. Kibel A, Iliopoulos O, DeCaprio JA, Kaelin WG Jr (1995) Binding of the von Hippel-Lindau tumor suppressor protein to elongin B and C. Science 269:1444–1446

    Article  PubMed  CAS  Google Scholar 

  18. Maxwell PH, Wiesener MS, Chang GW et al (1999) The tumor suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275

    Article  PubMed  CAS  Google Scholar 

  19. Cockman ME, Masson N, Mole DR et al (2000) Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J Biol Chem 275:25733–25741

    Article  PubMed  CAS  Google Scholar 

  20. Iliopoulos O, Levy AP, Jiang C et al (1996) Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci U S A 93:10595–10599

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Gruber M, Simon MC (2006) Hypoxia-inducible factors, hypoxia, and tumor angiogenesis. Curr Opin Hematol 13:169–174

    Article  PubMed  CAS  Google Scholar 

  22. Shen C, Kaelin WG Jr (2013) The VHL/HIF axis in clear cell renal carcinoma. Semin Cancer Biol 23:18–25

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Baba M, Hirai S, Yamada-Okabe H et al (2003) Loss of von Hippel-Lindau protein causes cell density dependent deregulation of cyclin D1 expression through hypoxia-inducible factor. Oncogene 22:2728–2738

    Article  PubMed  CAS  Google Scholar 

  24. Zatyka M, Fernandes da Silva N, Clifford SC et al (2002) Identification of cyclin D1 and other novel targets for the von Hippel-Lindau tumor suppressor gene by expression array analysis and investigation of cyclin D1 genotype as a modifier in von Hippel-Lindau disease. Cancer Res 62:3803–3811

    PubMed  CAS  Google Scholar 

  25. Schmelzle T, Hall MN (2000) TOR, a central controller of cell growth. Cell 103:253–262

    Article  PubMed  CAS  Google Scholar 

  26. Sarbassov DD, Guertin DA, Ali SM et al (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098–1101

    Article  PubMed  CAS  Google Scholar 

  27. Fingar DC, Richardson CJ, Tee AR et al (2004) mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4EBP1/eukaryotic translation factor 4E. Mol Cell Biol 24:200–216

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Hudson CC, Liu M, Chiang GG et al (2002) Regulation of hypoxia-inducible factor 1a expression and function by the mammalian target of rapamycin. Mol Cell Biol 22:7004–7014

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Thomas GV, Tran C, Mellinghoff IK et al (2005) Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med 12:122–127

    Article  PubMed  Google Scholar 

  30. Hudes GR (2009) Targeting mTOR in renal cell carcinoma. Cancer 115(Suppl 10):2313–2320

    Article  PubMed  CAS  Google Scholar 

  31. Porta C, Figlin R (2009) Phosphatidylinositol-3-kinase/Akt signaling pathway and kidney cancer, and the therapeutic potential of phosphatidylinositol-3-kinase/Akt inhibitors. J Urol 182:2569–2577

    Article  PubMed  CAS  Google Scholar 

  32. Robb VA, Karbowniczek M, Klein-Szanto AJ et al (2007) Activation of the mTOR signaling pathway in renal clear cell carcinoma. J Urol 177:346–352

    Article  PubMed  Google Scholar 

  33. Pantuck AJ, Seligson DB, Klatte T et al (2007) Prognostic relevance of the mTOR pathway in renal cell carcinoma. Cancer 109:2257–2267

    Article  PubMed  CAS  Google Scholar 

  34. Wilhelm SM, Carter C, Tang L et al (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109

    Article  PubMed  CAS  Google Scholar 

  35. Chang YS, Adnane L, Trail PA et al (2007) Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol 59:561–574

    Article  PubMed  CAS  Google Scholar 

  36. Porta C, Paglino C, Imarisio I, Ferraris E (2009) Sorafenib tosylate in advanced kidney cancer: past, present and future. Anticancer Drugs 20:409–415

    Article  PubMed  CAS  Google Scholar 

  37. Ratain MJ, Eisen T, Stadler WM et al (2006) Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 24:2505–2512

    Article  PubMed  CAS  Google Scholar 

  38. Escudier B, Eisen T, Stadler WM et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134

    Article  PubMed  CAS  Google Scholar 

  39. Escudier B, Eisen T, Stadler WM et al (2009) Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol 27:3312–3318

    Article  PubMed  CAS  Google Scholar 

  40. Beck J, Procopio G, Bajetta E et al (2011) Final results of the European Advanced Renal Cell Carcinoma Sorafenib (EU-ARCCS) expanded-access study: a large open-label study in diverse community settings. Ann Oncol 22:1812–1823

    Article  PubMed  CAS  Google Scholar 

  41. Stadler WM, Figlin RA, McDermott DF et al (2010) Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 116:1272–1280

    Article  PubMed  CAS  Google Scholar 

  42. Escudier B, Szczylik C, Hutson TE et al (2009) Randomized phase II trial of first-line treatment with sorafenib versus interferon alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol 27:1280–1289

    Article  PubMed  CAS  Google Scholar 

  43. Rini B, Szczylik C, Tannir NM et al (2012) AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney: a randomized, double-blind, placebo-controlled, phase 2 study. Cancer 118:6152–6161

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  44. Motzer RJ, Nosov D, Eisen T et al (2013) Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: results from a phase III randomized, open-label, multicenter trial. J Clin Oncol 31:3791–3799

    Article  PubMed  CAS  Google Scholar 

  45. Chow LQ, Eckhardt SG (2007) Sunitinib: from rational design to clinical efficacy. J Clin Oncol 25:884–896

    Article  PubMed  CAS  Google Scholar 

  46. Motzer RJ, Michaelson MD, Redman BG et al (2006) Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24:16–24

    Article  PubMed  CAS  Google Scholar 

  47. Motzer RJ, Rini BI, Bukowski RM et al (2006) Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295:2516–2524

    Article  PubMed  CAS  Google Scholar 

  48. Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124

    Article  PubMed  CAS  Google Scholar 

  49. Cella D, Li JZ, Cappelleri JC et al (2008) Quality of life in patients with metastatic renal cell carcinoma treated with sunitinib or interferon alfa: results from a phase III randomized trial. J Clin Oncol 26:3763–3769

    Article  PubMed  CAS  Google Scholar 

  50. Motzer RJ, Hutson TE, Tomczak P et al (2009) Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  51. Gore ME, Szczylik C, Porta C et al (2009) Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol 10:757–763

    Article  PubMed  CAS  Google Scholar 

  52. Motzer RJ, Hutson TE, Olsen MR et al (2012) Randomized phase II trial of sunitinib on an intermittent versus continuous dosing schedule as first-line therapy for advanced renal cell carcinoma. J Clin Oncol 30:1371–1377

    Article  PubMed  CAS  Google Scholar 

  53. Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ (2010) Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer Chemother Pharmacol 66:357–371

    Article  PubMed  CAS  Google Scholar 

  54. Ferrara N (2002) Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin Oncol 29(Suppl 16):10–14

    Article  PubMed  CAS  Google Scholar 

  55. Yang JC, Haworth L, Sherry RM et al (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  56. Escudier B, Pluzanska A, Koralewski P et al (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111

    Article  PubMed  Google Scholar 

  57. Rini BI, Halabi S, Rosenberg JE et al (2008) Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26:5422–5428

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  58. Melichar B, Koralewski P, Ravaud A et al (2008) First-line bevacizumab combined with reduced dose interferon-alpha2a is active in patients with metastatic renal cell carcinoma. Ann Oncol 19:1470–1476

    Article  PubMed  CAS  Google Scholar 

  59. Melichar B, Bracarda S, Matveev V et al (2013) A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN. Ann Oncol 24:2396–2402

    Article  PubMed  CAS  Google Scholar 

  60. Escudier B, Bellmunt J, Négrier S et al (2010) Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 28:2144–2150

    Article  PubMed  CAS  Google Scholar 

  61. Bracarda S, Bellmunt J, Melichar B et al (2011) Overall survival in patients with metastatic renal cell carcinoma initially treated with bevacizumab plus interferon-α2a and subsequent therapy with tyrosine kinase inhibitors: a retrospective analysis of the phase III AVOREN trial. BJU Int 107:214–219

    Article  PubMed  CAS  Google Scholar 

  62. Kumar R, Knick VB, Rudolph SK et al (2007) Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther 6:2012–2021

    Article  PubMed  CAS  Google Scholar 

  63. Hurwitz HI, Dowlati A, Saini S et al (2009) Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res 15:4220–4227

    Article  PubMed  CAS  Google Scholar 

  64. Hutson TE, Davis ID, Machiels JP et al (2010) Efficacy and safety of Pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 28:475–480

    Article  PubMed  CAS  Google Scholar 

  65. Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068

    Article  PubMed  CAS  Google Scholar 

  66. Motzer RJ, Hutson TE, Cella D et al (2013) Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369:722–731

    Article  PubMed  CAS  Google Scholar 

  67. Escudier B, Porta C, Bono P, et al (2014) Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol 32:1412–1418

    Google Scholar 

  68. Bukowski RM (2012) Third generation tyrosine kinase inhibitors and their development in advanced renal cell carcinoma. Front Oncol 2:13

    Article  PubMed Central  PubMed  Google Scholar 

  69. Rini BI, Escudier B, Tomczak P et al (2012) Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 378:1931–1939

    Article  Google Scholar 

  70. Motzer RJ, Escudier B, Tomczak P et al (2013) Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol 14:552–562

    Article  PubMed  CAS  Google Scholar 

  71. Hutson TE, Lesovoy V, Al-Shukri S et al (2013) Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol 14:1287–1294

    Article  PubMed  CAS  Google Scholar 

  72. Rini BI, Melichar B, Ueda T et al (2013) Axitinib with or without dose titration for first-line metastatic renal-cell carcinoma: a randomised double-blind phase 2 trial. Lancet Oncol 14:1233–1242

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  73. Buti S, Porta C (2013) Axitinib dose titration: what’s the limiting factor? Lancet Oncol 14:1152–1154

    Article  PubMed  Google Scholar 

  74. Dudkin L, Dilling MB, Cheshire PJ et al (2001) Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition. Clin Cancer Res 7:1758–1764

    PubMed  CAS  Google Scholar 

  75. Del Bufalo D, Ciuffreda L, Trisciuoglio D et al (2006) Antiangiogenic potential of the mammalian target of rapamycin inhibitor temsirolimus. Cancer Res 66:5549–5554

    Article  PubMed  Google Scholar 

  76. Atkins MB, Hidalgo M, Stadler WM et al (2004) Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 22:909–918

    Article  PubMed  CAS  Google Scholar 

  77. Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281

    Article  PubMed  CAS  Google Scholar 

  78. Dutcher JP, de Souza P, McDermott D et al (2009) Effect of temsirolimus versus interferon-alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies. Med Oncol 26:202–209

    Article  PubMed  CAS  Google Scholar 

  79. Hutson TE, Escudier B, Esteban E et al (2014) Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 32:760–767

    Google Scholar 

  80. Tanaka C, O’Reilly T, Kovarik JM et al (2008) Identifying optimal biologic doses of everolimus (RAD001) in patients with cancer based on the modeling of preclinical and clinical pharmacokinetic and pharmacodynamic data. J Clin Oncol 26:1596–1602

    PubMed  CAS  Google Scholar 

  81. Amato RJ, Jac J, Giessinger S, Saxena S, Willis JP (2009) A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer. Cancer 115:2438–2446

    Article  PubMed  CAS  Google Scholar 

  82. Motzer RJ, Escudier B, Oudard S et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456

    Article  PubMed  CAS  Google Scholar 

  83. Motzer RJ, Escudier B, Oudard S et al (2010) Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116:4256–4265

    Article  PubMed  CAS  Google Scholar 

  84. Porta C, Calvo E, Climent MA et al (2012) Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial. Eur Urol 61:826–833

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  85. Calvo E, Escudier B, Motzer RJ et al (2012) Everolimus in metastatic renal cell carcinoma: subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer 48:333–339

    Article  PubMed  CAS  Google Scholar 

  86. Bracarda S, Hutson TE, Porta C et al (2012) Everolimus in metastatic renal cell carcinoma patients intolerant to previous VEGFr-TKI therapy: a RECORD-1 subgroup analysis. Br J Cancer 106:1475–1480

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  87. Grünwald V, Karakiewicz PI, Bavbek SE et al (2012) An international expanded-access programme of everolimus: addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy. Eur J Cancer 48:324–332

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Piazzale C. Golgi, 19, 27100, Pavia, Italy

    Chiara Paglino, Palma Giglione & Camillo Porta M.D.

  2. Italian Nephro-Oncology Group/Gruppo Italiano di Oncologia Nefrologica (G.I.O.N.), Pavia, Italy

    Chiara Paglino, Laura Cosmai & Camillo Porta M.D.

  3. Nephrology and Dialysis, Istituti Ospitalieri Cremona, Cremona, Italy

    Laura Cosmai

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  1. Chiara Paglino
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  2. Laura Cosmai
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  3. Palma Giglione
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  4. Camillo Porta M.D.
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Correspondence to Camillo Porta M.D. .

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Editors and Affiliations

  1. Medical Oncology, University of Algarve, Faro, Portugal

    Ramon Andrade de Mello

  2. edificio 7, ala nascente, 3º andar, University of Algarve, Dept Cie Biomed edificio 7, ala nascente, 3º andar, Faro, Portugal

    Álvaro Tavares

  3. Medical Oncology, University of Athens, Athens, Greece

    Giannis Mountzios

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Paglino, C., Cosmai, L., Giglione, P., Porta, C. (2015). Renal Cell Carcinoma: From Molecular Biology to Targeted Therapies. In: de Mello, R., Tavares, Á., Mountzios, G. (eds) International Manual of Oncology Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-21683-6_23

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