nach oben

World Journal of Urology

Erschienen in:

01.07.2005 | Topic Paper

Novel approaches in the therapy of metastatic renal cell carcinoma

verfasst von: John S. Lam, John T. Leppert, Arie S. Belldegrun, Robert A. Figlin

Erschienen in: World Journal of Urology | Ausgabe 3/2005

Einloggen, um Zugang zu erhalten

Abstract

Renal cell carcinoma (RCC) is the most lethal of the common urologic malignancies, with approximately 40% of patients eventually dying of cancer progression. Approximately one third of patients present with metastatic disease, and up to 40% treated for localized disease have a recurrence. Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of RCC have paved the way for developments that may enhance early diagnosis, better predict tumor prognosis, and improve survival for RCC patients. The recent discovery of molecular tumor markers is expected to revolutionize the staging of RCC in the future and lead to the development of new therapies based on molecular targeting. Cytokine-based immunotherapy can be considered standard therapy in the treatment of metastatic RCC today. However, new therapies such as tumor vaccines, anti-angiogenesis agents, and small molecule inhibitors are being developed to improve efficacy and treat those patients who are unable to tolerate or are resistant to systemic immunotherapy. The aim of this review is to provide an update on current therapeutic approaches and targeted molecular therapy for metastatic RCC.

Antonia SJ, Seigne J, Diaz J, Muro-Cacho C, Extermann M, Farmelo MJ, Friberg M, Alsarraj M, Mahany JJ, Pow-Sang J, Cantor A, Janssen W (2002) Phase I trial of a B7–1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma. J Urol 167:1995–2000CrossRefPubMed

Assikis VJ, Daliani L, Pagliaro L, Wood C, Perez C, Logothetis C, Papandreou C, Hawkins ES, Srivastava PK (2003) Phase II study of an autologous tumor derived heat shock protein-peptide complex vaccine (HSPPC-96) for patients with metastatic renal cell carcinoma (mRCC). Proc Am Soc Clin Oncol 22:386

Atkins M, McDermott D, Mier J, Stanbridge E, Youmans A, Polivy A, Regran M, Connolly C, Febbo P, Upton M, Lechpammer M, Signoretti S (2004) Carbonic anhydrase IX (CAIX) expression predicts for renal cell cancer (RCC) patient response and survival to IL-2 therapy. Proc Am Soc Clin Oncol 23:383

Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR, Park Y, Liou SH, Marshall B, Boni JP, Dukart G, Sherman ML (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

Avigan DE, George DJ, Kantoff PW, Figlin RA, Kufe DW, Olencki TE, Vasconcelles MJ, Vasir BS, Xu Y, Bukowski RM (2004) Interim safety and efficacy results from a phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma. Proc Am Soc Clin Oncol 23:169

Baba M, Hirai S, Yamada-Okabe H, Hamada K, Tabuchi H, Kobayashi K, Kondo K, Yoshida M, Yamashita A, Kishida T, Nakaigawa N, Nagashima Y, Kubota Y, Yao M, Ohno S (2003) Loss of von Hippel-Lindau protein causes cell density dependent deregulation of CyclinD1 expression through hypoxia-inducible factor. Oncogene 22:2728–2738CrossRef

Bartlett JB, Michael A, Clarke IA, Dredge K, Nicholson S, Kristeleit H, Polychronis A, Pandha H, Muller GW, Stirling DI, Zeldis J, Dalgleish AG (2004) Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Br J Cancer 90:955–961CrossRef

Batist G, Patenaude F, Champagne P, Croteau D, Levinton C, Hariton C, Escudier B, Dupont E (2002) Neovastat (AE-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels. Ann Oncol 13:1259–1263CrossRef

Bevan P, Mala C, Kindler M, Siebels M, Oberneder R, Beck HJ (2004) Results of a phase I/II study with monoclonal antibody CG250 in combination with IFNα-2A in metastatic renal cell carcinoma patients. Proc Am Soc Clin Oncol 23:407

10.

Bindra RS, Vasselli JR, Stearman R, Linehan WM, Klausner RD (2002) VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells. Cancer Res 62:3014–3019PubMed

11.

Bleumer I, Knuth A, Oosterwijk E, Hofmann R, Varga Z, Lamers C, Kruit W, Melchior S, Mala C, Ullrich S, Mulder PD, Mulders PF, Beck J (2004) A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients. Br J Cancer 90:985–990CrossRef

12.

Bui MH, Seligson D, Han KR, Pantuck AJ, Dorey FJ, Huang Y, Horvath S, Leibovich BC, Chopra S, Liao SY, Stanbridge E, Lerman MI, Palotie A, Figlin RA, Belldegrun AS (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. Clin Cancer Res 9:802–811

13.

Bukowski RM (1997) Natural history and therapy of metastatic renal cell carcinoma: the role of interleukin-2. Cancer 80:1198–1220CrossRef

14.

Castillo M, Petit A, Mellado B, Palacin A, Alcover JB, Mallofre C (2004) C-kit expression in sarcomatoid renal cell carcinoma: potential therapy with imatinib. J Urol 171:2176–2180CrossRef

15.

Chang DZ, Olencki T, Budd GT, Peereboom D, Ganapathi R, Osterwalder B, Bukowski R (2001) Phase I trial of capecitabine in combination with interferon alpha in patients with metastatic renal cancer: toxicity and pharmacokinetics. Cancer Chemother Pharmacol 48:493–498

16.

Chia SK, Wykoff CC, Watson PH, Han C, Leek RD, Pastorek J, Gatter KC, Ratcliffe P, Harris AL (2001) Prognostic significance of a novel hypoxia-regulated marker, carbonic anhydrase IX, in invasive breast carcinoma. J Clin Oncol 19:3660–3668

17.

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

18.

Daliani DD, Papandreou CN, Thall PF, Wang X, Perez C, Oliva R, Pagliaro L, Amato R (2002) A pilot study of thalidomide in patients with progressive metastatic renal cell carcinoma. Cancer 95:758–765CrossRef

19.

Davidowitz EJ, Schoenfeld AR, Burk RD (2001) VHL induces renal cell differentiation and growth arrest through integration of cell-cell and cell-extracellular matrix signaling. Mol Cell Biol 21:865–874CrossRef

20.

Davis NB, Taber DA, Ansari RH, Ryan CW, George C, Vokes EE, Vogelzang NJ, Stadler WM (2004) Phase II trial of PS-341 in patients with renal cell cancer: a University of Chicago phase II consortium study. J Clin Oncol 22:115–119

21.

De Paulsen N, Brychzy A, Fournier MC, Klausner RD, Gnarra JR, Pause A, Lee S (2001) Role of transforming growth factor-alpha in von Hippel-Lindau (VHL)(−/−) clear cell renal carcinoma cell proliferation: a possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis. Proc Natl Acad Sci U S A 98:1387–1392CrossRef

22.

Divgi CR, Bander NH, Scott AM, O’Donoghue JA, Sgouros G, Welt S, Finn RD, Morrissey F, Capitelli P, Williams JM, Deland D, Nakhre A, Oosterwijk E, Gulec S, Graham MC, Larson SM, Old LJ (1998) Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. Clin Cancer Res 4:2729–2739

23.

Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031–1037CrossRefPubMed

24.

Eisen T, Boshoff C, Mak I, Sapunar F, Vaughan MM, Pyle L, Johnston SR, Ahern R, Smith IE, Gore ME (2000) Continuous low dose Thalidomide: a phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br J Cancer 82:812–817

25.

Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, Semenza GL (1999) Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2. Cancer Res 59:3915–3918

26.

Figlin RA (1999) Renal cell carcinoma: management of advanced disease. J Urol 161:381–387CrossRef

27.

Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JRJr, Munshi N, Crawford ED (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345:1655–1659CrossRefPubMed

28.

Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM, Semenza GL (2002) Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem 277:38205–38211CrossRef

29.

Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC (1995) Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 13:688–696

30.

Gitlitz BJ, Belldegrun AS, Zisman A, Chao DH, Pantuck AJ, Hinkel A, Mulders P, Moldawer N, Tso CL, Figlin RA (2003) A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma. J Immunother 26:412–419CrossRef

31.

Gitlitz BJ, Figlin RA (2003) Cytokine-based therapy for metastatic renal cell cancer. Urol Clin North Am 30:589–600

32.

Gnarra JR, Tory K, Weng Y, Schmidt L, Wei MH, Li H, Latif F, Liu S, Chen F, Duh FM et al. (1994) Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 7:85–90

33.

Grabmaier K, Vissers JL, De Weijert MC, Oosterwijk-Wakka JC, Van Bokhoven A, Brakenhoff RH, Noessner E, Mulders PA, Merkx G, Figdor CG, Adema GJ, Oosterwijk E (2000) Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250. Int J Cancer 85:865–870CrossRef

34.

Harris AL (2002) Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2:38–47.

35.

Hernandez JM, Bui MH, Han KR, Mukouyama H, Freitas DG, Nguyen D, Caliliw R, Shintaku PI, Paik SH, Tso CL, Figlin RA, Belldegrun AS (2003) Novel kidney cancer immunotherapy based on the granulocyte-macrophage colony-stimulating factor and carbonic anhydrase IX fusion gene. Clin Cancer Res 9:1906–1916

36.

Hernberg M, Virkkunen P, Bono P, Ahtinen H, Maenpaa H, joensuu H (2003) Interferon alfa-2b three times daily and thalidomide in the treatment of metastatic renal cell carcinoma. J Clin Oncol 21:3770–3776

37.

Holtl L, Rieser C, Papesh C, Ramoner R, Herold M, Klocker H, Radmayr C, Stenzl A, Bartsch G, Thurnher M (1999) Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells. J Urol 161:777–782CrossRefPubMed

38.

Medical Research Council Renal Cancer Collaborators (1999) Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Lancet 353:14–17CrossRef

39.

Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM (2002) Hsp90 regulates a von Hippel-Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J Biol Chem 277:29936–29944CrossRef

40.

Janzen NK, Kim HL, Figlin RA, Belldegrun AS (2003) Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 30:843–852

41.

Jemal A, Murray T, Ward E, Samuels A,Tiwari RC, Ghafoor A, Feur EJ, Thun MJ (2005) Cancer statistics, 2005. CA Cancer J Clin 55:10–30

42.

Jiang BH, Agani F, Passaniti A, Semenza GL (1997) V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Cancer Res 57:5328–5335

43.

Kaufman B, Scharf O, Arbeit J, Ashcroft M, Brown JM, Bruick RK, Chapman JD, Evans SM, Giaccia AJ, Harris AL, Huang E, Johnson R, Kaelin WJr, Koch CJ, Maxwell P, Mitchell J, Neckers L, Powis G, Rajendran J, Semenza GL, Simons J, Storkebaum E, Welch MJ, Whitelaw M, Melillo G, Ivy SP (2004) Proceedings of the Oxygen Homeostasis/Hypoxia Meeting. Cancer Res 64:3350–3356

44.

Knebelmann B, Ananth S, Cohen HT, Sukhatme VP (1998) Transforming growth factor alpha is a target for the von Hippel-Lindau tumor suppressor. Cancer Res 58:226–231

45.

Lam JS, Shvarts O, Leppert JT, Figlin RA, Belldegrun AS (2005) Renal cell carcinoma 2005: new frontiers in staging, prognostication, and targeted molecular therapy. J Urol (in press)

46.

Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (2002) Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295:858–861CrossRef

47.

Lebret T, Watson RW, Fitzpatrick JM (2003) Heat shock proteins: their role in urological tumors. J Urol 169:338–346CrossRef

48.

Lee Y, Vassilakos A, Feng N, Lam V, Xie H, Wang M, Jin H, Xiong K, Liu C, Wright J, Young A (2003) GTI-2040, an antisense agent targeting the small subunit component (R2) of human ribonucleotide reductase, shows potent antitumor activity against a variety of tumors. Cancer Res 63:2802–2811PubMed

49.

Linehan WM, Vasselli J, Srinivasan R, Walther MM, Merino M, Choyke P, Vocke C, Schmidt L, Isaacs JS, Glenn G, Toro J, Zbar B, Bottaro D, Neckers L (2004) Genetic basis of cancer of the kidney: disease-specific approaches to therapy. Clin Cancer Res 10:6282S-6289S

50.

Loncaster JA, Harris AL, Davidson SE, Logue JP, Hunter RD, Wycoff CC, Pastorek J, Ratcliffe PJ, Stratford IJ, West CM (2001) Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res 61:6394–6399PubMed

51.

Mahon PC, Hirota K, Semenza GL (2001) FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev 15:2675–2686CrossRef

52.

Makino Y, Kanopka A, Wilson WJ, Tanaka H, Poellinger L (2002) Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. J Biol Chem 277:32405–32408CrossRef

53.

Marshall JL, Rizvi N, Kauh J, Dahut W, Figuera M, Kang MH, Figg WD, Wainer I, Chaissang C, Li MZ, Hawkins MJ (2002) A phase I trial of depsipeptide (FR901228) in patients with advanced cancer. J Exp Ther Oncol 2:325–332CrossRef

54.

Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275CrossRefPubMed

55.

Mickisch GH, Garin A, Van Poppel H, De Prijck L, Sylvester R (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358:966–970CrossRefPubMed

56.

Motzer RJ, Amato R, Todd M, Hwu WJ, Cohen R, Baselga J, Muss H, Cooper M, Yu R, Ginsberg MS, Needle M (2003) Phase II trial of antiepidermal growth factor receptor antibody C225 in patients with advanced renal cell carcinoma. Invest New Drugs 21:99–101CrossRef

57.

Motzer RJ, Bacik J, Mariani T, Russo P, Mazumdar M, Reuter V (2002) Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology. J Clin Oncol 20:2376–2381

58.

Motzer RJ, Berg W, Ginsberg M, Russo P, Vuky J, Yu R, Bacik J, Mazumdar M (2002) Phase II trial of thalidomide for patients with advanced renal cell carcinoma. J Clin Oncol 20:302–306

59.

Motzer RJ, Rini BI, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, Zhu J, Kim ST, Baum C (2004) SUO11248, a novel tyrosine kinase inhibitor, shows antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma: results of a phase 2 trial. Proc Am Soc Clin Oncol 23:381

60.

Motzer RJ, Russo P (2000) Systemic therapy for renal cell carcinoma. J Urol 163:408–417PubMed

61.

Mukouyama H, Janzen NK, Hernandez JM, Lam JS, Caliliw R, Wang AY, Figlin RA, Belldegrun AS, Zeng G (2004) Generation of kidney cancer-specific antitumor immune responses using peripheral blood monocytes transduced with a recombinant adenovirus encoding carbonic anhydrase 9. Clin Cancer Res 10:1421–1429

62.

Na X, Wu G, Ryan CK, Schoen SR, Di’Santagnese PA, Messing EM (2003) Overproduction of vascular endothelial growth factor related to von Hippel-Lindau tumor suppressor gene mutations and hypoxia-inducible factor-1 alpha expression in renal cell carcinomas. J Urol 170:588–592CrossRef

63.

Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R, Frost P, Gibbons JJ, Wu H, Sawyers CL (2001) Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci U S A 98:10314–10319CrossRef

64.

Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS (2002) Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell 2:157–164CrossRef

65.

Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE, Pavletich N, Chau V, Kaelin WG (2000) Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol 2:423–427CrossRef

66.

Ohh M, Yauch RL, Lonergan KM, Whaley JM, Stemmer-Rachamimov AO, Louis DN, Gavin BJ, Kley N, Kaelin WGJr, Iliopoulos O (1998) The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix. Mol Cell 1:959–968CrossRef

67.

Olive PL, Aquino-Parsons C, MacPhail SH, Liao SY, Raleigh JA, Lerman MI, Stanbridge EJ (2001) Carbonic anhydrase 9 as an endogenous marker for hypoxic cells in cervical cancer. Cancer Res 61:8924–8929

68.

Oosterwijk E, Bander NH, Divgi CR, Welt S, Wakka JC, Finn RD, Carswell EA, Larson SM, Warnaar SO, Fleuren GJ et al. (1993) Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. J Clin Oncol 11:738–750

69.

Oosterwijk E, Ruiter DJ, Hoedemaeker PJ, Pauwels EK, Jonas U, Zwartendijk J, Warnaar SO (1986) Monoclonal antibody G 250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney. Int J Cancer 38:489–494

70.

Opavsky R, Pastorekova S, Zelnik V, Gibadulinova A, Stanbridge EJ, Zavada J, Kettmann R, Pastorek J (1996) Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. Genomics 33:480–487CrossRef

71.

Pantuck AJ, Belldegrun AS, Figlin RA (2001) Nephrectomy and interleukin-2 for metastatic renal-cell carcinoma. N Engl J Med 345:1711–1712CrossRef

72.

Pantuck AJ, Zeng G, Belldegrun AS, Figlin RA (2003) Pathobiology, prognosis, and targeted therapy for renal cell carcinoma: exploiting the hypoxia-induced pathway. Clin Cancer Res 9:4641–4652

73.

Pavlovich CP, Schmidt LS (2004) Searching for the hereditary causes of renal-cell carcinoma. Nat Rev Cancer 4:381–393CrossRef

74.

Phan GQ, Yang JC, Sherry RM, Hwu P, Topalian SL, Schwartzentruber DJ, Restifo NP, Haworth LR, Seipp CA, Freezer LJ, Morton KE, Mavroukakis SA, Duray PH, Steinberg SM, Allison JP, Davis TA, Rosenberg SA (2003) Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A 100:8372–8377

75.

Pisani P, Parkin DM, Bray F, Ferlay J (1999) Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83:18–29CrossRefPubMed

76.

Ratain MJ, Flaherty KT, Stadler WM, O’Dwyer P, Kaye S, Xiong H, Patnaik A, Gore M, Lee RJ, Eisen T (2004) Preliminary antitumor activity of BAY 43–9006 in metastatic renal cell carcinoma and other advanced refractory solid tumors in a phase II randomized discontinuation trail (RDT). Proc Am Soc Clin Oncol 23:381

77.

Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A (2000) Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14:34–44

78.

Rowinsky EK, Schwartz GH, Gollob JA, Thompson JA, Vogelzang NJ, Figlin R, Bukowski R, Haas N, Lockbaum P, Li YP, Arends R, Foon KA, Schwab G, Dutcher J (2004) Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol 22:3003–3015

79.

Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z, Lubensky I, Dean M, Allikmets R, Chidambaram A, Bergerheim UR, Feltis JT, Casadevall C, Zamarron A, Bernues M, Richard S, Lips CJ, Walther MM, Tsui LC, Geil L, Orcutt ML, Stackhouse T, Zbar B et al. (1997) Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 16:68–73CrossRef

80.

Schmidt L, Junker K, Nakaigawa N, Kinjerski T, Weirich G, Miller M, Lubensky I, Neumann HP, Brauch H, Decker J, Vocke C, Brown JA, Jenkins R, Richard S, Bergerheim U, Gerrard B, Dean M, Linehan WM, Zbar B (1999) Novel mutations of the MET proto-oncogene in papillary renal carcinomas. Oncogene 18:2343–2350CrossRef

81.

Schmidt L, Junker K, Weirich G, Glenn G, Choyke P, Lubensky I, Zhuang Z, Jeffers M, Vande Woude G, Neumann H, Walther M, Linehan WM, Zbar B (1998) Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. Cancer Res 58:1719–1722

82.

Semenza GL (2002) HIF-1 and tumor progression: pathophysiology and therapeutics. Trends Mol Med 8:S62–67CrossRef

83.

Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W (2003) Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425:307–311PubMed

84.

Stebbing J, Benson C, Eisen T, Pyle L, Smalley K, Bridle H, Mak I, Sapunar F, Ahern R, Gore ME (2001) The treatment of advanced renal cell cancer with high-dose oral thalidomide. Br J Cancer 85:953–958CrossRef

85.

Su Z, Dannull J, Heiser A, Yancey D, Pruitt S, Madden J, Coleman D, Niedzwiecki D, Gilboa E, Vieweg J (2003) Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res 63:2127–2133PubMed

86.

Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, Vierimaa O, Aittomaki K, Hietala M, Sistonen P, Paetau A, Salovaara R, Herva R, Launonen V, Aaltonen LA (2002) Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 30:406–410CrossRef

87.

Tso CL, Zisman A, Pantuck A, Calilliw R, Hernandez JM, Paik S, Nguyen D, Gitlitz B, Shintaku PI, De Kernion J, Figlin R, Belldegrun A (2001) Induction of G250-targeted and T-cell-mediated antitumor activity against renal cell carcinoma using a chimeric fusion protein consisting of G250 and granulocyte/monocyte-colony stimulating factor. Cancer Res 61:7925–7933

88.

Turner KJ, Crew JP, Wykoff CC, Watson PH, Poulsom R, Pastorek J, Ratcliffe PJ, Cranston D, Harris AL (2002) The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer. Br J Cancer 86:1276–1282CrossRef

89.

Tyers M, Rottapel R (1999) VHL: a very hip ligase. Proc Natl Acad Sci U S A 96:12230–12232CrossRef

90.

Uemura H, Nakagawa Y, Yoshida K, Saga S, Yoshikawa K, Hirao Y, Oosterwijk E (1999) MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas. Br J Cancer 81:741–746CrossRef

91.

Vissers JL, De Vries IJ, Engelen LP, Scharenborg NM, Molkenboer J, Figdor CG, Oosterwijk E, Adema GJ (2002) Renal cell carcinoma-associated antigen G250 encodes a naturally processed epitope presented by human leukocyte antigen-DR molecules to CD4(+) T lymphocytes. Int J Cancer 100:441–444CrossRef

92.

Vissers JL, De Vries IJ, Schreurs MW, Engelen LP, Oosterwijk E, Figdor CG, Adema GJ (1999) The renal cell carcinoma-associated antigen G250 encodes a human leukocyte antigen (HLA)-A2.1-restricted epitope recognized by cytotoxic T lymphocytes. Cancer Res 59:5554–5559PubMed

93.

Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434CrossRef

94.

Yang JC, Sherry RM, Steinberg SM, Topalian SL, Schwartzentruber DJ, Hwu P, Seipp CA, Rogers-Freezer L, Morton KE, White DE, Liewehr DJ, Merino MJ, Rosenberg SA (2003) Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 21:3127–3132CrossRefPubMed

95.

Yao M, Yoshida M, Kishida T, Nakaigawa N, Baba M, Kobayashi K, Miura T, Moriyama M, Nagashima Y, Nakatani Y, Kubota Y, Kondo K (2002) VHL tumor suppressor gene alterations associated with good prognosis in sporadic clear-cell renal carcinoma. J Natl Cancer Inst 94:1569–1575

96.

Yeo EJ, Chun YS, Cho YS, Kim J, Lee JC, Kim MS, Park JW (2003) YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst 95:516–525

97.

Zavada J, Zavadova Z, Pastorek J, Biesova Z, Jezek J, Velek J (2000) Human tumour-associated cell adhesion protein MN/CA IX: identification of M75 epitope and of the region mediating cell adhesion. Br J Cancer 82:1808–1813

98.

Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, Simons JW, Semenza GL (2000) Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 60:1541–1545PubMed

Titel: Novel approaches in the therapy of metastatic renal cell carcinoma
verfasst von: John S. Lam
John T. Leppert
Arie S. Belldegrun
Robert A. Figlin
Publikationsdatum: 01.07.2005
Verlag: Springer-Verlag
Erschienen in: World Journal of Urology / Ausgabe 3/2005
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-004-0466-0

Neu im Fachgebiet Urologie

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

Stufenschema weist Prostatakarzinom zuverlässig nach

22.04.2024 Prostatakarzinom Nachrichten

Erst PSA-Test, dann Kallikrein-Score, schließlich MRT und Biopsie – ein vierstufiges Screening-Schema kann die Zahl der unnötigen Prostatabiopsien erheblich reduzieren: Die Hälfte der Männer, die in einer finnischen Studie eine Biopsie benötigten, hatte einen hochgradigen Tumor.

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

20.04.2024 EAU 2024 Kongressbericht

Beim chronischen Harnwegsinfekt bei Frauen wird bisher meist eine Antibiotikaprophylaxe eingesetzt. Angesichts der zunehmenden Antibiotikaresistenz erweist sich das Antiseptikum Methenamin-Hippurat als vielversprechende Alternative, so die Auswertung einer randomisierten kontrollierten Studie.

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2005

Nonmyeloablative allogeneic stem cell transplantation in metastatic renal cell carcinoma: a new therapeutic option or just a clinical experiment?

Surgery for metastatic renal cell cancer

New challenges and chances in the treatment of metastatic renal cell carcinoma

A new technique combining both polypropylene and vaginal wall sling procedures: can it minimize the risk of urethral and vaginal erosion occurring with synthetic materials?