Review: Targeted therapy in renal cancer

Therapeutic Advances in Medical Oncology

Volumn 1, Issue 3, 2009, Pages 183-205

  Dorff, Tanya B ^a   Goldkorn, Amir ^a   Quinn, David I ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

bevacizumab; everolimus; renal cell carcinoma; sorafenib; sunitinib; temsirolimus

Indexed keywords

ALPHA INTERFERON; ANTIDIARRHEAL AGENT; ANTINEOPLASTIC AGENT; AXITINIB; BEVACIZUMAB; EVEROLIMUS; IMATINIB; INTERLEUKIN 2; LANOLIN; PAZOPANIB; PLACEBO; PLATELET DERIVED GROWTH FACTOR; SORAFENIB; SUNITINIB; TEMSIROLIMUS; VASCULOTROPIN; VON HIPPEL LINDAU PROTEIN;

ACUTE TOXICITY; ADJUVANT THERAPY; ANEMIA; ANOREXIA; ASTHENIA; CANCER COMBINATION CHEMOTHERAPY; CANCER RISK; CANCER SURVIVAL; CLEAR CELL CARCINOMA; CLINICAL TRIAL; COLORECTAL CANCER; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG MEGADOSE; DRUG TARGETING; FATIGUE; FOLLOW UP; GASTROINTESTINAL STROMAL TUMOR; GENE MUTATION; GENE SILENCING; HAIR DEPIGMENTATION; HAND FOOT SYNDROME; HEART LEFT VENTRICLE FAILURE; HIGH RISK POPULATION; HUMAN; HYPERGLYCEMIA; HYPERLIPIDEMIA; HYPERTENSION; HYPERTHYROIDISM; HYPOPHOSPHATEMIA; HYPOTHYROIDISM; IMMUNOTHERAPY; IN VITRO STUDY; IN VIVO STUDY; KIDNEY CARCINOMA; LEUKOPENIA; LIVER CELL CARCINOMA; LOW DRUG DOSE; LUNG NON SMALL CELL CANCER; MOLECULAR BIOLOGY; MONOTHERAPY; MUCOSA INFLAMMATION; NAIL DISEASE; NAUSEA; NEPHRECTOMY; NEUTROPENIA; NONHUMAN; OPTIMAL DRUG DOSE; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PATIENT CARE; PNEUMONIA; PREDICTION; PRIORITY JOURNAL; PROTEINURIA; QUALITY OF LIFE; RASH; REVIEW; SKIN MANIFESTATION; SKIN TOXICITY; STOMATITIS; THROMBOCYTOPENIA; TREATMENT WITHDRAWAL;

EID: 77953453516     PISSN: 17588340     EISSN: None     Source Type: Journal    
DOI: 10.1177/1758834009349119     Document Type: Review

References (205)

1. Aaltomaa, S., Lipponen, P., Ala-Opas, M., Eskelinen, M., Syrjanen, K. and Kosma, V.M. ( 1999) Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival. Br J Cancer 80: 2001-2007.
2. Abrams, T.J., Lee, L.B., Murray, L.J., Pryer, N.K. and Cherrington, J.M. ( 2003) Su11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther 2: 471-478.
3. Amin, M.B., Tamboli, P., Javidan, J., Stricker, H., Venturina, M.D., Deshpande, A. et al. (2002) Prognostic impact of histologic subtyping of adult renal epithelial neoplasms: an experience of 405 cases. Am J Surg Pathol 26: 281-291.
4. Atkins, M., Regan, M., Mcdermott, D., Mier, J., Stanbridge, E., Youmans, A. et al. (2005) Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res 11: 3714-3721.
5. Atkins, M.B., Hidalgo, M., Stadler, W.M., Logan, T.F., Dutcher, J.P., Hudes, G.R. 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.
6. Atkins, M.B., Sparano, J., Fisher, R.I., Weiss, G.R., Margolin, K.A., Fink, K.I. et al. (1993) Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. J Clin Oncol 11: 661-670.
7. Awada, A., Hendlisz, A., Gil, T., Bartholomeus, S., Mano, M., de Valeriola, D. et al. (2005) Phase I safety and pharmacokinetics of bay 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer 92: 1855-1861.
8. Balzer-Hass, N.S., Flaherty, K.T., Uzzo, R., Kane, C.J., Wood, C.G. and Jewett, M.A.S. ( 2007) Phase III randomized study of adjuvant sunitinib malate versus sorafenib in patients with resected renal cell carcinoma; Nct 00326898: ECOG/Intergroup E 2805.
9. Bensalah, K., Pantuck, A.J., Crepel, M., Verhoest, G., Mejean, A., Valeri, A. et al. (2008) Prognostic variables to predict cancer-related death in incidental renal tumours. BJU Int 102: 1376-1380.
10. Blancher, C., Moore, J.W., Robertson, N. and Harris, A.L. ( 2001) Effects of RAS and Von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3’-kinase/Akt signaling pathway. Cancer Res 61: 7349-7355.
11. Bracarda, S., Porta, C., Boni, C., Santoro, A., Artioli, F., Di Bartolomeo, C. et al. (2007) Randomized prospective phase II trial of two schedules of sorafenib daily and interferon-A2a (IFN) in metastatic renal cell carcinoma (rapsody): GOIRC (Italian Oncology Group for Clinical Research) Study 0681. J Clin Oncol, ASCO Annual Meeting Proceedings, Vol. 25: Chicago, IL.
12. Brauch, H., Weirich, G., Brieger, J., Glavac, D., Rodl, H., Eichinger, M. et al. (2000) VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation. Cancer Res 60: 1942-1948.
13. Brown, L.F., Berse, B., Jackman, R.W., Tognazzi, K., Manseau, E.J., Dvorak, H.F. et al. (1993) Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 143: 1255-1262.
14. Brugarolas, J.B., Vazquez, F., Reddy, A., Sellers, W.R. and Kaelin Jr, W.G. ( 2003) TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 4: 147-158.
15. Bukowski, R., Cella, D., Gondek, K. and Escudier, B. ( 2007c) Effects of sorafenib on symptoms and quality of life: results from a large randomized placebo-controlled study in renal cancer. Am J Clin Oncol 30: 220-227.
16. Bukowski, R.M., Eisen, T., Szczylik, C., Stadler, W.M., Simantov, R., Shan, M. et al. (2007 a) Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: survival and biomarker analysis. J Clin Oncol, ASCO Annual Meeting Proceedings 25: 5023.
17. Bukowski, R.M., Kabbinavar, F.F., Figlin, R.A., Flaherty, K., Srinivas, S., Vaishampayan, U. et al. (2007 b) Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol 25: 4536-4541.
18. Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Gertsenstein, M. et al. (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF Allele. Nature 380: 435-439.
19. Chan, A.S., Leung, S.Y., Wong, M.P., Yuen, S.T., Cheung, N., Fan, Y.W. et al. (1998) Expression of vascular endothelial growth factor and its receptors in the anaplastic progression of astrocytoma, oligodendroglioma, and ependymoma. Am J Surg Pathol 22: 816-826.
20. Cheng, S.Y., Huang, H.J., Nagane, M., Ji, X.D., Wang, D., Shih, C.C. et al. (1996) Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. Proceedings of the National Academy of Sciences of the United States of America 93: 8502-8507.
21. Choueiri, T.K., Garcia, J.A., Elson, P., Khasawneh, M., Usman, S., Golshayan, A.R. et al. (2007) Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. Cancer 110: 543-550.
22. Choueiri, T.K., Vaziri, S.A., Jaeger, E., Elson, P., Wood, L., Bhalla, I.P. et al. (2008) Von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma. J Urol 180: 860-865.
23. Chow, W.H., Devesa, S.S., Warren, J.L. and Fraumeni Jr, J.F. ( 1999) Rising incidence of renal cell cancer in the United States. J Am Med Assoc 281: 1628-1631.
24. Chu, T.F., Rupnick, M.A., Kerkela, R., Dallabrida, S.M., Zurakowski, D., Nguyen, L. et al. (2007) Cardiotoxicity associated with TKI sunitinib. Lancet 370: 2011-2019.
25. Clark, J.I., Atkins, M.B., Urba, W.J., Creech, S., Figlin, R.A., Dutcher, J.P. et al. (2003) Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a cytokine working group randomized trial. J Clin Oncol 21: 3133-3140.
26. Clark, J.W., Eder, J.P., Ryan, D., Lathia, C. and Lenz, H.J. ( 2005) Safety and pharmacokinetics of the dual action RAF kinase and vascular endothelial growth factor receptor inhibitor, bay 43-9006, in patients with advanced, refractory solid tumors. Clin Cancer Res 11: 5472-5480.
27. Clifford, S.C., Astuti, D., Hooper, L., Maxwell, P.H., Ratcliffe, P.J. and Maher, E.R. ( 2001) The pVHLassociated SCF ubiquitin ligase complex: Molecular genetic analysis of elongin B and C, RBXL and HIF-1alpha in renal cell carcinoma. Oncogene 20: 5067-5074.
28. Clifford, S.C. and Maher, E.R. ( 2001) Von Hippel-Lindau disease: Clinical and molecular perspectives. Adv Cancer Res 82: 85-105.
29. Collaborators, M.R.C.R.C. (1999) Interferon-alpha and survival in metastatic renal carcinoma: Early results of a randomised controlled trial. Lancet 353: 14-17.
30. Coppin, C., Porzsolt, F., Awa, A., Kumpf, J., Coldman, A. and Wilt, T. ( 2005) Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev CD001425.
31. David, K.A., Milowsky, M.I. and Nanus, D.M. ( 2006) Chemotherapy for non-clear-cell renal cell carcinoma. Clin Genitourin Cancer 4: 263-268.
32. Decastro, G.J. and Mckiernan, J.M. ( 2008) Epidemiology, clinical staging, and presentation of renal cell carcinoma. Urol Clin North Am 35: 581-592.
33. Del Bufalo, D., Ciuffreda, L., Trisciuoglio, D., Desideri, M., Cognetti, F., Zupi, G. et al. (2006) Antiangiogenic potential of the mammalian target of rapamycin inhibitor temsirolimus. Cancer Res 66: 5549-5554.
34. Demetri, G.D., van Oosterom, A.T., Garrett, C.R., Blackstein, M.E., Shah, M.H., Verweij, J. et al. (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. Lancet 368: 1329-1338.
35. Dosquet, C., Coudert, M.C., Lepage, E., Cabane, J. and Richard, F. ( 1997) Are angiogenic factors, cytokines, and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma? Clin Cancer Res 3: 2451-2458.
36. Duan, D.R., Pause, A., Burgess, W.H., Aso, T., Chen, D.Y., Garrett, K.P. et al. (1995) Inhibition of transcription elongation by the VHL tumor suppressor protein. Science 269: 1402-1406.
37. Dudkin, L., Dilling, M.B., Cheshire, P.J., Harwood, F.C., Hollingshead, M., Arbuck, S.G. et al. (2001) Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition. Clin Cancer Res 7: 1758-1764.
38. Dulaimi, E., DeCaceres, I.I., Uzzo, R.G., Al-Saleem, T., Greenberg, T., Polascik, R.E. et al. (2004) Promoter hypermethylation profile of kidney cancer. Clin Cancer Res 10: 3972-3979.
39. Dutcher, J., Atkins, M.B., Margolin, K., Weiss, G., Clark, J., Sosman, J. et al. (2001) Kidney cancer: the cytokine working group experience (1986-2001): Part II. management of II-2 toxicity and studies with other cytokines. Med Oncol 18: 209-219.
40. Dutcher, J.P., Logan, T., Gordon, M., Sosman, J., Weiss, G., Margolin, K. et al. (2000) Phase II trial of interleukin 2, interferon alpha, and 5-fluorouracil in metastatic renal cell cancer: A cytokine working group study. Clin Cancer Res 6: 3442-3450.
41. Dutcher, J.P., Wilding, G., Hudes, G.R., Stadler, W.M., Kim, S., Tarazi, J.C. et al. (2008) Sequential axitinib (Ag-013736) therapy of patients (Pts) with metastatic clear cell renal cell cancer (RCC) refractory to sunitinib and sorafenib, cytokines and sorafenib, or sorafenib alone. J Clin Oncol, ASCO Annual Meeting Proceedings, Vol. 26: Chicago, IL.
42. Dvorak, H.F., Brown, L.F., Detmar, M. and Dvorak, A.M. ( 1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. American Journal of Pathology 146: 1029-1039.
43. Eisen, T. ( 2007) Sorafenib in treating patients at risk of relapse after undergoing surgery to remove kidney; Nct 00492258; Mrc-Re05-Sorce; Eudract Id 2006-006079-19; Eu-20734.
44. Escudier, B., Choueiri, T.K., Oudard, S., Szczylik, C., Negrier, S., Ravaud, A. et al. (2007 a) Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: New paradigm from a large phase III trial with shark cartilage extract Ae 941. J Urol 178: 1901-1905.
45. Escudier, B., Eisen, T., Stadler, W.M., Szczylik, C., Oudard, S., Siebels, M. et al. (2007 b) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356: 125-134.
46. Escudier, B., Eisen, T., Stadler, W.M., Szczylik, C., Oudard, S., Staehler, M. et al. (2009 a) 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.
47. Escudier, B., Pluzanska, A., Koralewski, P., Ravaud, A., Bracarda, S., Szczylik, C. et al. (2007 c) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial. Lancet 370: 2103-2111.
48. Escudier, B., Szczylik, C., Hutson, T.E., Demkow, T., Staehler, M., Rolland, F. et al. (2009 b) 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.
49. Faivre, S., Delbaldo, C., Vera, K., Robert, C., Lozahic, S., Lassau, N. et al. (2006) Safety, pharmacokinetic, and antitumor activity of Su 11248, a novel oral multitarget TKI, in patients with cancer. J Clin Oncol 24: 25-35.
50. Feldman, D.R., Baum, M.S., Ginsberg, M.S., Hassoun, H., Flombaum, C.D., Velasco, S. et al. (2009) Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 27: 1432-1439.
51. Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, K.S. et al. (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380: 439-442.
52. Fidler, I.J. and Ellis, L.M. ( 1994) The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 79: 185-188.
53. Figlin, R.A., Belldegrun, A., Moldawer, N., Zeffren, J. and Dekernion, J. ( 1992) Concomitant administration of recombinant human interleukin-2 and recombinant interferon alfa-2a: an active outpatient regimen in metastatic renal cell carcinoma. J Clin Oncol 10: 414-421.
54. Figlin, R.A., Thompson, J.A., Bukowski, R.M., Vogelzang, N.J., Novick, A.C., Lange, P. et al. (1999) Multicenter, randomized, phase III trial of Cd8(+) tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol 17: 2521-2529.
55. Finke, J.H., Rayman, P., George, R., Tannenbaum, C.S., Kolenko, V., Uzzo, R. et al. (2001) Tumor-induced sensitivity to apoptosis in T cells from patients with renal cell carcinoma: role of nuclear factor-kappab suppression. Clin Cancer Res 7: 940s-946s.
56. Fisher, R.I., Coltman Jr, C.A., Doroshow, J.H., Rayner, A.A., Hawkins, M.J., Mier, J.W. et al. (1988) Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial. Ann Intern Med 108: 518-523.
57. Fisher, R.I., Rosenberg, S.A. and Fyfe, G. ( 2000) Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am 6 Suppl 1: S55-S57.
58. Flaherty, K.T. and Mcdermott, D.F. ( 2007) The BeST trial: A randomized phase II study of VEGF, RAF kinase, and mTOR combination targeted therapy (CTT) with bevacizumab, sorafenib and temsirolimus in advanced renal cell carcinoma. Nct00378703; ECOG-E2804.
59. Flanigan, R.C., Salmon, S.E., Blumenstein, B.A., Bearman, S.I., Roy, V., Mcgrath, P.C. et al. (2001) Nephrectomy followed by interferon alpha-2b compared with interferon alpha-2b alone for metastatic renal-cell cancer. N Engl J Med 345: 1655-1659.
60. Fong, G.H., Rossant, J., Gertsenstein, M. and Breitman, M.L. ( 1995) Role of the FLT-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376: 66-70.
61. Furge, K.A., Tan, M.H., Dykema, K., Kort, E., Stadler, W., Yao, X. et al. (2007) Identification of deregulated oncogenic pathways in renal cell carcinoma: an integrated oncogenomic approach based on gene expression profiling. Oncogene 26: 1346-1350.
62. Gabrilovich, D., Ishida, T., Oyama, T., Ran, S., Kravtsov, V., Nadaf, S. et al. (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92: 4150-4166.
63. Gabrilovich, D.I., Ishida, T., Nadaf, S., Ohm, J.E. and Carbone, D.P. ( 1999) Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin Cancer Res 5: 2963-2970.
64. George, D.J. and Kaelin Jr, W.G. ( 2003) The Von Hippel-Lindau protein, vascular endothelial growth factor, and kidney cancer. N Engl J Med 349: 419-421.
65. Gitlitz, B.J., Hoffman, D.M., Moldawer, N., Belldegrun, A. and Figlin, R.A. ( 2001) Treatment of metastatic renal cell carcinoma with high-dose bolus interleukin-2 in a non-intensive care unit: an analysis of 124 consecutively treated patients. Cancer J 7: 112-120.
66. Gnarra, J.R., Duan, D.R., Weng, Y., Humphrey, J.S., Chen, D.Y., Lee, S. et al. (1996 a) Molecular cloning of the Von Hippel-Lindau tumor suppressor gene and its role in renal carcinoma. Biochim Biophys Acta 1242: 201-210.
67. Gnarra, J.R., Zhou, S., Merrill, M.J., Wagner, J.R., Krumm, A., Papavassiliou, E. et al. (1996 b) Post-transcriptional regulation of vascular endothelial growth factor MRNA by the product of the VHL tumor suppressor gene. Proc Natl Acad Sci U S A 93: 10589-10594.
68. Gobé, G., Rubin, M., Williams, G., Sawczuk, I. and Buttyan, R. ( 2002) Apoptosis and expression of Bcl-2, Bcl-XL, and Bax in renal cell carcinomas. Cancer Invest 20: 324-332.
69. Gollob, J.A., Rathmell, W.K., Richmond, T.M., Marino, C.B., Miller, E.K., Grigson, G. et al. (2007) Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J Clin Oncol 25: 3288-3295.
70. Gomella, L.G., Anglard, P., Sargent, E.R., Robertson, C.N., Kasid, A. and Linehan, W.M. ( 1990) Epidermal growth factor receptor gene analysis in renal cell carcinoma. J Urol 143: 191-193.
71. Grumont, R.J., Rourke, I.J., O’Reilly, L.A., Strasser, A., Miyake, K., Sha, W. et al. (1998) B lymphocytes differentially use the Rel and nuclear factor kappaB 1 (Nf-kappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogen-activated cells. J Exp Med 187: 663-674.
72. Guba, M., Von Breitenbuch, P., Steinbauer, M., Koehl, G., Flegel, S., Hornung, M. et al. (2002) Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: Involvement of vascular endothelial growth factor. Nat Med 8: 128-135.
73. Gunaratnam, L., Morley, M., Franovic, A., de Paulsen, N., Mekhail, K., Parolin, D.A. et al. (2003) HIF activates the TGF-alpha/EGF-R growth stimulatory pathway in VHL/renal cell carcinoma cells. J Biol Chem 27: 27.
74. Gunningham, S.P., Currie, M.J., Han, C., Turner, K., Scott, P.A., Robinson, B.A. et al. (2001) Vascular endothelial growth factor-B and vascular endothelial growth factor-C expression in renal cell carcinomas: regulation by the Von Hippel-Lindau gene and hypoxia. Cancer Res 61: 3206-3211.
75. Haitel, A., Wiener, H.G., Neudert, B., Marberger, M. and Susani, M. ( 2001) Expression of the cell cycle proteins P21, P27, and PRB in clear cell renal cell carcinoma and their prognostic significance. Urology 58: 477-481.
76. Hanahan, D. and Weinberg, R.A. ( 2000) The hall-marks of cancer. Cell 100: 57-70.
77. Hansen, W.J., Ohh, M., Moslehi, J., Kondo, K., Kaelin, W.G. and Welch, W.J. ( 2002) Diverse effects of mutations in exon II of the Von Hippel-Lindau (VHL) tumor suppressor gene on the interaction of pVHL with the cytosolic chaperonin and pVHLdependent ubiquitin ligase activity. Mol Cell Biol 22: 1947-1960.
78. Hara, S., Oya, M., Mizuno, R., Horiguchi, A., Marumo, K. and Murai, M. ( 2005) Akt activation in renal cell carcinoma: contribution of a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor. Ann Oncol 16: 928-933.
79. Hedberg, Y., Davoodi, E., Roos, G., Ljungberg, B. and Landberg, G. ( 1999) Cyclin-D1 expression in human renal-cell carcinoma. Int J Cancer 84: 268-272.
80. Hofmockel, G., Riess, S., Bassukas, I.D. and Dammrich, J. ( 1997) Epidermal growth factor family and renal cell carcinoma: expression and prognostic impact. Eur Urol 31: 478-484.
81. Hon, W.C., Wilson, M.I., Harlos, K., Claridge, T.D., Schofield, C.J., Pugh, C.W. et al. (2002) Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL. Nature 417: 975-978.
82. Horiguchi, A., Oya, M., Uchida, A., Marumo, K. and Murai, M. ( 2003) Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma. J Urol 169: 710-713.
83. Huang, A., Fone, P.D., Gandour-Edwards, R., White, R.W. and Low, R.K. ( 1999) Immunohistochemical analysis of bcl-2 protein expression in renal cell carcinoma. J Urol 162: 610-613.
84. Hudes, G., Carducci, M., Tomczak, P., Dutcher, J., Figlin, R., Kapoor, A. et al. (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356: 2271-2281.
85. Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W. et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335-2342.
86. Hurwitz, H.I., Dowlati, A., Saini, S., Savage, S., Suttle, A.B., Gibson, D.M. et al. (2009) Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res 15: 4220-4227.
87. Hutson, T.E. ( 2007) Temsirolimus and sorafenib as second-line therapy in patients with advanced RCC who failed first-line sunitinib: Nct 00474786 : Wyeth 3066k1-306404.
88. Hutson, T.E., Davis, I.D., Machiels, J.P., de Souza, P.L., Hong, B.F., Rottey, S. et al. (2007) Pazopanib (Gw786034) is active in metastatic renal cell carcinoma (RCC): interim results of a phase II randomized discontinuation trial (RDT). J Clin Oncol (Meeting Abstracts) 25: 5031.
89. Hutson, T.E. and Figlin, R.A. ( 2007) Evolving role of novel targeted agents in renal cell carcinoma. Oncology (Williston Park) 21: 1175-1180.
90. Hutson, T.E. and Quinn, D.I. ( 2005) Cytokine therapy: a standard of care for metastatic renal cell carcinoma? Clin Genitourin Cancer 4: 181-186.
91. Iliopoulos, O., Levy, A.P., Jiang, C., Kaelin Jr, W.G. and Goldberg, M.A. ( 1996) Negative regulation of hypoxia-inducible genes by the Von Hippel-Lindau protein. Proc Natl Acad Sci U S A 93: 10595-10599.
92. Iwai, K., Yamanaka, K., Kamura, T., Minato, N., Conaway, R.C., Conaway, J.W. et al. (1999) Identification of the Von Hippel-Lindau tumor-suppressor protein as part of an active E 3 ubiquitin ligase complex. Proc Natl Acad Sci U S A 96: 12436-12441.
93. Jacobsen, J., Rasmuson, T., Grankvist, K. and Ljungberg, B. ( 2000) Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol 163: 343-347.
94. Jonasch, E., Corn, P., Ashe, R.G., Do, K. and Tannir, N.M. ( 2007) Randomized phase II study of sorafenib with or without low-dose IFN in patients with metastatic tenal cell carcinoma. J Clin Oncol, ASCO Annual Meeting Proceedings, Vol. 25: Chiacgo, IL.
95. Kaelin Jr, W.G. ( 2009) Treatment of kidney cancer: insights provided by the VHL tumor-suppressor protein. Cancer 115: 2262-2272.
96. Kallakury, B.V., Karikehalli, S., Haholu, A., Sheehan, C.E., Azumi, N. and Ross, J.S. ( 2001) Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma. Clin Cancer Res 7: 3113-3119.
97. Karakiewicz, P.I., Briganti, A., Chun, F.K., Trinh, Q.D., Perrotte, P., Ficarra, V. et al. (2007) Multi-institutional validation of a new renal cancer-specific survival nomogram. J Clin Oncol 25: 1316-1322.
98. Kenerson, H.L., Aicher, L.D., True, L.D. and Yeung, R.S. ( 2002) Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors. Cancer Res 62: 5645-5650.
99. Khakoo, A.Y., Kassiotis, C.M., Tannir, N., Plana, J.C., Halushka, M., Bickford, C. et al. (2008) Heart failure associated with sunitinib malate: a multitargeted receptor TKI. Cancer 112: 2500-2508.
100. Kim, H.J., Park, J.K. and Kim, Y.G. ( 1999) Suppression of NF-Kappab activation in normal T cells by supernatant fluid from human renal cell carcinomas. J Korean Med Sci 14: 299-303.
101. Kim, K.J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H.S. et al. (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841-844.
102. Krieg, M., Haas, R., Brauch, H., Acker, T., Flamme, I. and Plate, K.H. ( 2000) Up-regulation of hypoxia-inducible factors HIF-1alpha and HIF-2alpha under normoxic conditions in renal carcinoma cells by Von Hippel-Lindau tumor suppressor gene loss of function. Oncogene 19: 5435-5443.
103. Krishnan, B. and Truong, L.D. ( 2002) Renal epithelial neoplasms: the diagnostic implications of electron microscopic study in 55 cases. Hum Pathol 33: 68-79.
104. Leung, S.Y., Chan, A.S., Wong, M.P., Yuen, S.T., Cheung, N. and Chung, L.P. ( 1997) Expression of vascular endothelial growth factor and its receptors in pilocytic astrocytoma. Am J Surg Pathol 21: 941-950.
105. Li, Q. and Verma, I.M. ( 2002) NF-Kappab regulation in the immune system. Nat Rev Immunol 2: 725-734.
106. Li, X., Liu, J., Park, J.K., Hamilton, T.A., Rayman, P., Klein, E. et al. (1994) T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity: a preliminary report. Cancer Res 54: 5424-5429.
107. Li, Y., Wang, M.N., Li, H., King, K.D., Bassi, R., Sun, H. et al. (2002) Active immunization against the vascular endothelial growth factor receptor FLK 1 inhibits tumor angiogenesis and metastasis. J Exp Med 195: 1575-1584.
108. Llovet, J.M., Ricci, S., Mazzaferro, V., Hilgard, P., Gane, E., Blanc, J.F. et al. (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378-390.
109. Mack, F.A., Rathmell, W.K., Arsham, A.M., Gnarra, J., Keith, B. and Simon, M.C. ( 2003) Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth. Cancer Cell 3: 75-88.
110. Maher, E.R. and Kaelin Jr, W.G. ( 1997) Von Hippel-Lindau disease. Medicine ( Baltimore) 76: 381-391.
111. Majumder, P.K., Febbo, P.G., Bikoff, R., Berger, R., Xue, Q., McMahon, L.M. et al. (2004) mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 10: 594-601.
112. Mathew, A., Devesa, S.S., Fraumeni Jr, J.F. and Chow, W.H. ( 2002) Global increases in kidney cancer incidence, 1973-1992. Eur J Cancer Prev 11: 171-178.
113. Maxwell, P.H., Wiesener, M.S., Chang, G.W., Clifford, S.C., Vaux, E.C., Cockman, M.E. et al. (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399: 271-275.
114. Clement, J.M. and McDermott, D.F. (2009) The high-dose aldesleukin (IL-2) ‘select’ trial: a trial designed to prospectively validate predictive models of response to high dose IL-2 treatment in patients with metastatic renal cell carcinoma. Clin Genitourin Cancer 7: E7-E9.
115. McDermott, D.F., Regan, M.M., Clark, J.I., Flaherty, L.E., Weiss, G.R., Logan, T.F. et al. (2005) Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 23: 133-141.
116. McDonald, P.P., Bald, A. and Cassatella, M.A. ( 1997) Activation of the NF-Kappab pathway by inflammatory stimuli in human neutrophils. Blood 89: 3421-3433.
117. Mekhail, T.M., Abou-Jawde, R.M., Boumerhi, G., Malhi, S., Wood, L., Elson, P. et al. (2005) Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23: 832-841.
118. Melichar, B., Koralewski, P., Ravaud, A., Pluzanska, A., Bracarda, S., Szczylik, C. 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.
119. Mendel, D.B., Laird, A.D., Xin, X., Louie, S.G., Christensen, J.G., Li, G. et al. (2003) In vivo antitumor activity of Su11248, a novel TKI targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9: 327-337.
120. Messing, E.M., Manola, J., Wilding, G., Propert, K., Fleischmann, J., Crawford, E.D. et al. (2003) Phase III study of interferon alfa-a as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol 21: 1214-1222.
121. Mickisch, G.H., Garin, A., van Poppel, H., de Prijck, L. and 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: 966-970.
122. Migita, T., Oda, Y., Naito, S. and Tsuneyoshi, M. ( 2002) Low expression of P 27(KIP1) is associated with tumor size and poor prognosis in patients with renal cell carcinoma. Cancer 94: 973-979.
123. Motzer, R.J., Bacik, J., Mariani, T., Russo, P., Mazumdar, M. and Reuter, V. ( 2002) Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear-cell histology. J Clin Oncol 20: 2376-2381.
124. Motzer, R.J., Bacik, J., Schwartz, L.H., Reuter, V., Russo, P., Marion, S. et al. (2004) Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 22: 454-463.
125. Motzer, R.J., Bukowski, R.M., Figlin, R.A., Hutson, T.E., Michaelson, M.D., Kim, S.T. et al. (2008 a) Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma. Cancer 113: 1552-1558.
126. Motzer, R.J., Escudier, B., Oudard, S., Hutson, T.E., Porta, C., Bracarda, S. et al. (2008 b) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372: 449-456.
127. Motzer, R.J., Hudes, G.R., Curti, B.D., Mcdermott, D.F., Escudier, B.J., Negrier, S. et al. (2007 c) Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol 25: 3958-3964.
128. Motzer, R.J., Hutson, T.E., Tomczak, P., Michaelson, M.D., Bukowski, R.M., Oudard, S. 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.
129. Motzer, R.J., Hutson, T.E., Tomczak, P., Michaelson, M.D., Bukowski, R.M., Rixe, O. et al. (2007 b) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356: 115-124.
130. Motzer, R.J., Mazumdar, M., Bacik, J., Berg, W., Amsterdam, A. and Ferrara, J. ( 1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17: 2530-2540.
131. Motzer, R.J., Mazumdar, M., Bacik, J., Russo, P., Berg, W.J. and Metz, E.M. ( 2000) Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma. J Clin Oncol 18: 1928-1935.
132. Motzer, R.J., Michaelson, M.D., Redman, B.G., Hudes, G.R., Wilding, G., Figlin, R.A. et al. (2006 a) 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.
133. Motzer, R.J., Michaelson, M.D., Rosenberg, J., Bukowski, R.M., Curti, B.D., George, D.J. et al. (2007 a) Sunitinib efficacy against advanced renal cell carcinoma. J Urol 178: 1883-1887.
134. Motzer, R.J., Rini, B.I., Bukowski, R.M., Curti, B.D., George, D.J., Hudes, G.R. et al. (2006 b) Sunitinib in patients with metastatic renal cell carcinoma. J Am Med Assoc 295: 2516-2524.
135. Na, X., Wu, G., Ryan, C.K., Schoen, S.R., Di’santagnese, P.A. and Messing, E.M. ( 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: 588-592.
136. Negrier, S., Caty, A., Lesimple, T., Douillard, J.Y., Escudier, B., Rossi, J.F. et al. (2000 a) Treatment of patients with metastatic renal carcinoma with a combination of subcutaneous interleukin-2 and interferon alpha with or without fluorouracil. Groupe Francais D’immunotherapie, Federation Nationale Des Centres de Lutte Contre Le Cancer. J Clin Oncol 18: 4009-4015.
137. Negrier, S., Escudier, B., Gomez, F., Douillard, J.Y., Ravaud, A., Chevreau, C. et al. (2002) Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais D’immunotherapie. Ann Oncol 13: 1460-1468.
138. Negrier, S., Escudier, B., Lasset, C., Douillard, J.Y., Savary, J., Chevreau, C. et al. (1998) Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais D’immunotherapie. N Engl J Med 338: 1272-1278.
139. Negrier, S., Maral, J., Drevon, M., Vinke, J., Escudier, B. and Philip, T. ( 2000b) Long-term follow-up of patients with metastatic renal cell carcinoma treated with intravenous recombinant interleukin-2 in Europe. Cancer J Sci Am 6(Suppl 1): S93-S98.
140. Negrier, S., Perol, D., Ravaud, A., Chevreau, C., Bay, J.O., Delva, R. et al. (2007) Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial. Cancer 110: 2366-2369.
141. Niethammer, A.G., Xiang, R., Becker, J.C., Wodrich, H., Pertl, U., Karsten, G. et al. (2002) A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med 8: 1369-1375.
142. O’Donnell, A., Faivre, S., Burris, H.A., Rea, D., Papadimitrakopoulou, V., Shand, N. et al. (2008) Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol 26: 1588-1595.
143. Oda, H., Nakatsuru, Y. and Ishikawa, T. ( 1995) Mutations of the P 53 gene and P 53 protein overexpression are associated with sarcomatoid transformation in renal cell carcinomas. Cancer Res 55: 658-662.
144. Ohm, J.E., Gabrilovich, D.I., Sempowski, G.D., Kisseleva, E., Parman, K.S., Nadaf, S. et al. (2003) VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood 101: 4878-4886.
145. Osusky, K.L., Hallahan, D.E., Fu, A., Ye, F., Shyr, Y. and Geng, L. ( 2004) The receptor TKI Su 11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels. Angiogenesis 7: 225-233.
146. Oyama, T., Ran, S., Ishida, T., Nadaf, S., Kerr, L., Carbone, D.P. et al. (1998) Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol 160: 1224-1232.
147. Pantuck, A.J., Seligson, D.B., Klatte, T., Yu, H., Leppert, J.T., Moore, L. et al. (2007) Prognostic relevance of the mTOR pathway in renal cell carcinoma: implications for molecular patient selection for targeted therapy. Cancer 109: 2257-2267.
148. Patard, J.J., Dorey, F.J., Cindolo, L., Ficarra, A.D.L.T., Tostain, J. et al. (2004 a) Symptoms as well as tumor size provide prognostic information on patients with localized renal tumors. J Urol 172: 2167-2171.
149. Patard, J.J., Kim, H.L., Lam, J.S., Dorey, F.J., Pantuck, A.J., Zisman, A. et al. (2004 b) Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol 22: 3316-3322.
150. Patel, P.H., Chadalavada, R.S., Ishill, N.M., Patil, S., Reuter, V.E., Motzer, R.J. et al. (2008) Hypoxia-inducible factor (HIF) 1{Alpha} and 2{Alpha} levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC). J Clin Oncol (Meeting Abstracts) 26: 5008.
151. Prowse, A.H., Webster, A.R., Richards, F.M., Richard, S., Olschwang, S., Resche, F. et al. (1997) Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors. Am J Hum Genet 60: 765-771.
152. Ratain, M.J., Eisen, T., Stadler, W.M., Flaherty, K.T., Kaye, S.B., Rosner, G.L. 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.
153. Ratain, M.J., Flaherty, K.T., Stadler, W.M., O’Dwyer, P., Kaye, S., Xiong, H. et al. (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 trial, Proc Am Soc Clin Oncol, Vol. 23: New Orleans, LA.
154. Reiter, R.E., Anglard, P., Liu, S., Gnarra, J.R. and Linehan, W.M. ( 1993) Chromosome 17p deletions and P 53 mutations in renal cell carcinoma. Cancer Res 53: 3092-3097.
155. Rini, B.I. ( 2008a) Axitinib (Ag 013736) as second line therapy for metastatic renal cell cancer, a phase III trial with sorafenib; Nct 00678392, A 4061032, Axis Trial.
156. Rini, B.I. ( 2008b) Renal cancer - commentary, J Clin Oncol, ASCO Annual Meeting Proceedings, Vol. 26: Chicago, IL.
157. Rini, B.I., Halabi, S., Rosenberg, J.E., Stadler, W.M., Vaena, D.A., Ou, S.S. 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.
158. Rini, B.I. and Small, E.J. ( 2005) Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma. J Clin Oncol 23: 1028-1043.
159. Rini, B.I., Tamaskar, I., Shaheen, P., Salas, R., Garcia, J., Wood, L. et al. (2007) Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 99: 81-83.
160. Rixe, O., Bukowski, R.M., Michaelson, M.D., Wilding, G., Hudes, G.R., Bolte, O. et al. (2007) Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol 8: 975-984.
161. Robert, C., Soria, J.C., Spatz, A., Le Cesne, A., Malka, D., Pautier, P. et al. (2005) Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol 6: 491-500.
162. Ronnen, E.A., Kondagunta, G.V., Ishill, N., Spodek, L., Russo, P., Reuter, V. et al. (2006) Treatment outcome for metastatic papillary renal cell carcinoma patients. Cancer 107: 2617-2621.
163. Rosenberg, S.A., Lotze, M.T., Yang, J.C., Linehan, W.M., Seipp, C., Calabro, S. et al. (1989) Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol 7: 1863-1874.
164. Rosenberg, S.A., Yang, J.C., Topalian, S.L., Schwartzentruber, D.J., Weber, J.S., Parkinson, D.R. et al. (1994) Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. J Am Med Assoc 271: 907-913.
165. Rosner, G.L., Stadler, W. and Ratain, M.J. ( 2002) Randomized discontinuation design: application to cytostatic antineoplastic agents. J Clin Oncol 20: 4478-4484.
166. Ryan, C.W., Goldman, B.H., Lara Jr, P.N., Mack, P.C., Beer, T.M., Tangen., M. et al. (2007) Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group. J Clin Oncol 25: 3296-3301.
167. Ryan, C.W., Vogelzang, N.J. and Stadler, W.M. ( 2002) A phase II trial of intravenous gemcitabine and 5-fluorouracil with subcutaneous interleukin-2 and interferon-alpha in patients with metastatic renal cell carcinoma. Cancer 94: 2602-2609.
168. Sandler, A., Gray, R., Perry, M.C., Brahmer, J., Schiller, J.H., Dowlati, A. et al. (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355: 2542-2550.
169. Sargent, E.R., Gomella, L.G., Belldegrun, A., Linehan, W.M. and Kasid, A. ( 1989) Epidermal growth factor receptor gene expression in normal human kidney and renal cell carcinoma. J Urol 142: 1364-1368.
170. Senger, D.R., van de Water, L., Brown, L.F., Nagy, J.A., Yeo, K.T., Yeo, T.K. et al. (1993) Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer & Metastasis Reviews 12: 303-324.
171. Shalaby, F., Rossant, J., Yamaguchi, T.P., Gertsenstein, M., Wu, X.F., Breitman, M.L. et al. (1995) Failure of blood-island formation and vasculogenesis in FLK-1-deficient mice. Nature 376: 62-66.
172. Simons, J.P., Aaronson, N.K., Vansteenkiste, J.F., Ten Velde, G.P., Muller, M.J., Drenth, B.M. et al. (1996) Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study. J Clin Oncol 14: 1077-1084.
173. Sionov, R.V. and Haupt, Y. ( 1999) The cellular response to P53: the decision between life and death. Oncogene 18: 6145-6157.
174. Slaton, J.W., Inoue, K., Perrotte, P., El-Naggar, A.K., Swanson, D.A., Fidler, I.J. et al. (2001) Expression levels of genes that regulate metastasis and angiogenesis correlate with advanced pathological stage of renal cell carcinoma. Am J Pathol 158: 735-743.
175. Sonpavde, G. and Hutson, T.E. ( 2008) New treatments for metastatic renal cell carcinoma. Clin Genitourin Cancer 6: S29-S36.
176. Sternberg, C.N., Szczylik, C., Lee, E., Salman, P.V., Mardiak, J., Davis, I.D. et al. (2009) A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). J Clin Oncol (Meeting Abstracts) 27: 5021.
177. Strumberg, D., Awada, A., Hirte, H., Clark, J.W., Seeber, S., Piccart, P. et al. (2006) Pooled safety analysis of bay 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: is rash associated with treatment outcome? Eur J Cancer 42: 548-556.
178. Strumberg, D., Richly, H., Hilger, R.A., Schleucher, N., Korfee, S., Tewes, M. et al. (2005) Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J Clin Oncol 23: 965-972.
179. Stumm, G., Eberwein, S., Rostock-Wolf, S., Stein, H., Pomer, S., Schlegel, J. et al. (1996) Concomitant overexpression of the EGFR and ERBB-2 genes in renal cell carcinoma (RCC) is correlated with dedifferentiation and metastasis. Int J Cancer 69: 17-22.
180. Sun, L., Liang, C., Shirazian, S., Zhou, Y., Miller, T., Cui, J. et al. (2003) Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3z)-ylidenemethyl]-2,4-dimethyl-1h-pyrrole-3-carboxylic acid
181. (2-diethylaminoethyl)amide, a novel TKI targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J Med Chem 46: 1116-1119.
182. Takahashi, A., Sasaki, H., Kim, S.J., Tobisu, K., Kakizoe, T., Tsukamoto, T. et al. (1994) Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res 54: 4233-4237.
183. Takahashi, M., Yang, X.J., Sugimura, J., Backdahl, J., Tretiakova, M., Qian, C.N. et al. (2003) Molecular subclassification of kidney tumors and the discovery of new diagnostic markers. Oncogene 22: 6810-6818.
184. Tamaskar, I., Choueiri, T.K., Sercia, L., Rini, B., Bukowski, R. and Zhou, M. ( 2007) Differential expression of caveolin-1 in renal neoplasms. Cancer 110: 776-782.
185. Tanaka, C., O’Reilly, T., Kovarik, J.M., Shand, N., Hazell, K., Judson, I. 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.
186. Telli, M.L., Witteles, R.M., Fisher, G.A. and Srinivas, S. ( 2008) Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate. Ann Oncol 19: 1613-1618.
187. Textor, S.C., Margolin, K., Blayney, D., Carlson, J. and Doroshow, J. ( 1987) Renal, volume, and hormonal changes during therapeutic administration of recombinant interleukin-2 in man. Am J Med 83: 1055-1061.
188. Thrash-Bingham, C.A. and Tartof, K.D. ( 1999) HIFalpha: a natural antisense transcript overexpressed in human renal cancer and during hypoxia. J Natl Cancer Inst 91: 143-151.
189. Turner, J.S., Cheung, E.M., George, J. and Quinn, D.I. ( 2007) Pain management, supportive and palliative care in patients with renal cell carcinoma. BJU Int 99: 1305-1312.
190. Uchida, T., Gao, J.P., Wang, C., Jiang, S.X., Muramoto, M., Satoh, T. et al. (2002) Clinical significance of P53, Mdm2, and Bcl-2 proteins in renal cell carcinoma. Urology 59: 615-620.
191. Uhlman, D.L., Nguyen, P., Manivel, J.C., Zhang, G., Hagen, K., Fraley, E. et al. (1995) Epidermal growth factor receptor and transforming growth factor alpha expression in papillary and nonpapillary renal cell carcinoma: correlation with metastatic behavior and prognosis. Clin Cancer Res 1: 913-920.
192. Uhlman, D.L., Nguyen, P.L., Manivel, J.C., Aeppli, D., Resnick, J.M., Fraley, E.E. et al. (1994) Association of immunohistochemical staining for P 53 with metastatic progression and poor survival in patients with renal cell carcinoma. J Natl Cancer Inst 86: 1470-1475.
193. Upton, M.P., Parker, R.A., Youmans, A., Mcdermott, D.F. and Atkins, M.B. ( 2005) Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy. J Immunother 28: 488-495.
194. Uzzo, R.G., Clark, P.E., Rayman, P., Bloom, T., Rybicki, L., Novick, A.C. et al. (1999) Alterations in NF kappab activation in T lymphocytes of patients with renal cell carcinoma. J Natl Cancer Inst 91: 718-721.
195. Uzzo, R.G., Rayman, P., Kolenko, V., Clark, P.E., Cathcart, M.K., Bloom, T. et al. (1999) Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappab activation in T cells. J Clin Invest 104: 769-776.
196. Veronese, M.L., Mosenkis, A., Flaherty, K.T., Gallagher, M., Stevenson, J.P., Townsend, R.R. et al. (2006) Mechanisms of hypertension associated with Bay 43-9006. J Clin Oncol 24: 1363-1369.
197. Vogelzang, N.J. and Stadler, W.M. ( 1998) Kidney cancer. Lancet 352: 1691-1696.
198. Walpole, E.T., Dutcher, J.P., Sparano, J., Gucalp, R., Einzig, A., Paietta, E. et al. (1993) Survival after phase II treatment of advanced renal cell carcinoma with taxol or high-dose interleukin-2. J Immunother 13: 275-281.
199. Wilhelm, S.M., Carter, C., Tang, L., Wilkie, D., Mcnabola, A., Rong, H. 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.
200. Wykoff, C.C., Sotiriou, C., Cockman, M.E., Ratcliffe, P.J., Maxwell, P., Liu, E. et al. (2004) Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D 1 is a VHL target gene. Br J Cancer 90: 1235-1243.
201. Yagoda, A., Abi-Rached, B. and Petrylak, D. ( 1995) Chemotherapy for advanced renal-cell carcinoma: 1983-1993. Semin Oncol 22: 42-60.
202. Yang, J.C., Haworth, L., Sherry, R.M., Hwu, P., Schwartzentruber, D.J., Topalian, S.L. 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.
203. Yap, T.A. and Eisen, T.G. ( 2006) Adjuvant therapy of renal cell carcinoma. Clin Genitourin Cancer 5: 120-130.
204. Yee, K.W., Zeng, Z., Konopleva, M., Verstovsek, S., Ravandi, F., Ferrajoli, A. et al. (2006) Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (Rad001) in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res 12: 5165-5173.
205. Zisman, A., Pantuck, A.J., Dorey, F., Said, J.W., Shvarts, O., Quintana, D. et al. (2001) Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol 19: 1649-1657.