qui, en activant mTOR (mammalian Target Of Rapamycin) va favoriser la carcinogenèse par une augmentation de la synthèse des protéines nécessaires au développement tumoral Cette voie est située en aval des récepteurs à activité tyrosine kinase (VEGFR par exemple). L'activation d'un RTK induit l'activation de la phosphatidylinositol-3-kinase (PI3K) PI3K est un hétérodimère constitué de deux sous-unités : une sous-unité régulatrice p85 et une sous-unité catalytique p110 (Dreyer C, 2008). PI3K activé va phosphoryler le phosphatidyl-inosiltol-diphosphate (PIP2) en phosphatidyl-inositol-triphosphate (PIP3) ce qui permet l', 2008. ,
phosphatase and tensin homologue deleted on chromosome 10) permet la régulation de cette voie en s'opposant à la phosphorylation de PIP2 par PI3K, ce qui a pour conséquence l'inhibition d'AKT. Une diminution de l'expression de PTEN a été retrouvée dans de nombreux cancers chez l'homme dont le cancer du rein, 2009. ,
angiopoïétine 2 pourraient bloquer efficacement l'angiogenèse et par extension, la croissance tumorale. Il est cependant difficile de limiter l'action d'un anticorps sur l'angiopoïétine 2 sans action sur l'angiopoïétine 1 de par la similitude des deux facteurs. L'AMG-386 ,
Il est nécessaire d'espacer la prise de ces médicaments d'au moins deux heures avec la prise de sunitinib (RCP Sutent®) ,
Sutent® est un médicament soumis à prescription hospitalière. Sa prescription est réservée aux spécialistes en oncologie ou en hématologie ou aux médecins compétents en cancérologie ,
C'est pourquoi les anti-H2 et les inhibiteurs de la pompe à protons (IPP) peuvent diminuer les concentrations de sorafénib ,
Il est nécessaire d'espacer la prise de ces médicaments d'au moins deux heures avec la prise de sorafénib ,
SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer, Mol. Cancer Ther, vol.2, issue.5, pp.471-479, 2003. ,
Complete Remission With Tyrosine Kinase Inhibitors in Renal Cell Carcinoma, Journal of Clinical Oncology, vol.30, issue.5, pp.482-489 ,
DOI : 10.1200/JCO.2011.37.2516
Renal Cell Carcinoma Lung Metastases Surgery: Pathologic Findings and Prognostic Factors, The Annals of Thoracic Surgery, vol.84, issue.4, pp.1114-1134, 2007. ,
DOI : 10.1016/j.athoracsur.2007.04.118
Molecular mechanisms of tumor vascularization, Critical Reviews in Oncology/Hematology, vol.54, issue.1 ,
DOI : 10.1016/j.critrevonc.2004.11.006
Combination Targeted Therapy With Sorafenib and Bevacizumab Results in Enhanced Toxicity and Antitumor Activity, Journal of Clinical Oncology, vol.26, issue.22 ,
DOI : 10.1200/JCO.2007.10.8332
Angiogenesis inhibition: review of the activity of sorafenib, sunitinib and bevacizumab], Bull Cancer, vol.97, pp.29-43, 2010. ,
Tyrosine kinase receptors as attractive targets of cancer therapy, Critical Reviews in Oncology/Hematology, vol.50, issue.1, pp.23-38, 2004. ,
DOI : 10.1016/j.critrevonc.2003.08.004
Development of Second-Generation VEGFR Tyrosine Kinase Inhibitors: Current Status, Current Oncology Reports, vol.9, issue.2, pp.103-114, 2011. ,
DOI : 10.1200/JCO.2005.03.6723
Invasive growth: a MET-driven genetic programme for cancer and stem cells, Nature Reviews Cancer, vol.16, issue.8, pp.637-682, 2006. ,
DOI : 10.1038/ncponc0225
Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms, Nature Reviews Cancer, vol.91, issue.8, pp.579-91, 2004. ,
DOI : 10.1002/1097-0215(200002)9999:9999<::AID-IJC1053>3.0.CO;2-T
Neuropilin-1 Upholds Dedifferentiation and Propagation Phenotypes of Renal Cell Carcinoma Cells by Activating Akt and Sonic Hedgehog Axes, Cancer Research, vol.68, issue.21 ,
DOI : 10.1158/0008-5472.CAN-08-2614
Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell, pp.299-309, 2005. ,
Quality of Life in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib or Interferon Alfa: Results From a Phase III Randomized Trial, Journal of Clinical Oncology, vol.26, issue.22, pp.3763-3772, 2008. ,
DOI : 10.1200/JCO.2007.13.5145
Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome. Blood, nov, vol.15110, issue.10, pp.3729-3763, 2007. ,
Engineering Antibodies for Clinical Applications in Cancer, Tumor Biology, vol.25, issue.1-2, pp.91-99, 2004. ,
DOI : 10.1159/000077727
Prospective Evaluation of Analgesic Use and Risk of Renal Cell Cancer, Archives of Internal Medicine, vol.171, issue.16, pp.1487-93, 2011. ,
DOI : 10.1001/archinternmed.2011.356
Obesity, Hypertension, and the Risk of Kidney Cancer in Men, New England Journal of Medicine, vol.343, issue.18, pp.1305-1316, 20002. ,
DOI : 10.1056/NEJM200011023431804
Pathology and Molecular Pathogenesis of Renal Cell Carcinoma, European Urology Supplements, vol.5, issue.8, pp.573-582, 2006. ,
DOI : 10.1016/j.eursup.2006.03.005
EORTC-GU group expert opinion on metastatic renal cell cancer, European Journal of Cancer, vol.45, issue.5, pp.765-73, 2009. ,
DOI : 10.1016/j.ejca.2008.12.010
Morphologic typing of papillary renal cell carcinoma: Comparison of growth kinetics and patient survival in 66 cases, Human Pathology, vol.32, issue.6 ,
DOI : 10.1053/hupa.2001.24984
Topics in mTOR pathway and its inhibitors]. Bull Cancer, pp.87-94, 2009. ,
Signalling pathways in renal-cell carcinoma: from the molecular biology to the future therapy], Bull Cancer, vol.97, pp.5-15, 2010. ,
URL : https://hal.archives-ouvertes.fr/inserm-00480057
Tie receptors and their angiopoietin ligands are context-dependent regulators of vascular remodeling, Experimental Cell Research, vol.312, issue.5, pp.630-671, 2006. ,
DOI : 10.1016/j.yexcr.2005.09.002
Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Annals of Oncology, vol.72, issue.9, pp.137-139, 2010. ,
DOI : 10.1200/JCO.2007.13.3223
Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma, New England Journal of Medicine, vol.356, issue.2, pp.125-159, 2007. ,
DOI : 10.1056/NEJMoa060655
Sequential therapy in renal cell carcinoma. Cancer, 2009. ,
Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial, The Lancet, vol.370, issue.9605, pp.2103-2114, 2007. ,
DOI : 10.1016/S0140-6736(07)61904-7
Randomized Phase II Trial of First-Line Treatment With Sorafenib Versus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma, Journal of Clinical Oncology, vol.27, issue.8, pp.1280-1289, 2009. ,
DOI : 10.1200/JCO.2008.19.3342
Phase I Trial of Bevacizumab Plus Escalated Doses of Sunitinib in Patients With Metastatic Renal Cell Carcinoma, Journal of Clinical Oncology, vol.27, issue.9 ,
DOI : 10.1200/JCO.2008.19.0108
The biology of VEGF and its receptors, Nature Medicine, vol.99, issue.21, pp.669-76, 2003. ,
DOI : 10.1073/pnas.152324099
Analysis of PTEN and HIF-1alpha and correlation with efficacy in patients with advanced renal cell carcinoma treated with temsirolimus versus interferon-alpha. Cancer, pp.3651-60, 2009. ,
[Management of side effects associated with antiangiogenic treatment in renal cell carcinoma], Bull Cancer, vol.97, pp.73-82, 2010. ,
Somatic mutations of the von Hippel ??? Lindau disease tumour suppressor gene in non-familial clear cell renal carcinoma, Human Molecular Genetics, vol.3, issue.12 ,
DOI : 10.1093/hmg/3.12.2169
Targeted therapies: sequential and combined treatments], Bull Cancer, vol.97, pp.65-71, 2010. ,
Progress and contrasts of the development of tivozanib for therapy of kidney cancer, Expert Opinion on Pharmacotherapy, vol.34, issue.10, pp.2915-2937, 2011. ,
DOI : 10.1358/dof.2009.034.10.1417872
Phase II Trial of Bevacizumab and Everolimus in Patients With Advanced Renal Cell Carcinoma, Journal of Clinical Oncology, vol.28, issue.13, pp.2131-2137, 2010. ,
DOI : 10.1200/JCO.2009.26.3152
Hallmarks of Cancer: The Next Generation, Cell, vol.144, issue.5, pp.646-74 ,
DOI : 10.1016/j.cell.2011.02.013
Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma, New England Journal of Medicine, vol.356, issue.22, pp.2271-81, 2007. ,
DOI : 10.1056/NEJMoa066838
Renal cell carcinoma of endstage renal disease: a histopathologic and molecular genetic study, J. Am. Soc. Nephrol, vol.7, issue.11, pp.2461-2469, 1996. ,
Renal cell carcinoma in relation to cigarette smoking: Meta-analysis of 24 studies, International Journal of Cancer, vol.128, issue.1, pp.101-109, 2005. ,
DOI : 10.1093/oxfordjournals.bmb.a011531
Sequential use of targeted agents in the treatment of renal cell carcinoma, Critical Reviews in Oncology/Hematology, vol.77, issue.1, pp.48-62, 2011. ,
DOI : 10.1016/j.critrevonc.2010.07.018
Gamma Knife radiosurgery for brainstem metastases: the UCSF experience, Journal of Neuro-Oncology, vol.46, issue.2, pp.195-205, 2008. ,
DOI : 10.1016/0360-3016(90)90421-F
Birt-Hogg-Dub?? syndrome: mapping of a novel hereditary neoplasia gene to chromosome 17p12-q11.2, Oncogene, vol.20, issue.37, pp.5239-5281, 2001. ,
DOI : 10.1111/j.1600-0560.1977.tb00920.x
Declining mortality from kidney cancer in Europe, Annals of Oncology, vol.15, issue.7, pp.1130-1135, 2004. ,
DOI : 10.1093/annonc/mdh270
Everolimus (RAD001) and solid tumours: a 2008 summary]. Bull Cancer, pp.1205-1216, 2008. ,
Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell, mars, vol.315, issue.3, pp.167-70, 2009. ,
DOI : 10.1016/j.ccr.2009.02.007
URL : https://doi.org/10.1016/j.ccr.2009.02.007
2004 WHO Classification of the Renal Tumors of the Adults, European Urology, vol.49, issue.5, pp.798-805, 2006. ,
DOI : 10.1016/j.eururo.2005.11.035
Regression of Metastatic Renal Cell Carcinoma After Cytoreductive Nephrectomy, The Journal of Urology, vol.150, issue.2, pp.463-469, 1993. ,
DOI : 10.1016/S0022-5347(17)35514-3
Randomized Phase III Trial of High-Dose Interleukin-2 Versus Subcutaneous Interleukin-2 and Interferon in Patients With Metastatic Renal Cell Carcinoma, Journal of Clinical Oncology, vol.23, issue.1, pp.133-174, 2005. ,
DOI : 10.1200/JCO.2005.03.206
Survival and Prognostic Stratification of 670 Patients With Advanced Renal Cell Carcinoma, Journal of Clinical Oncology, vol.17, issue.8, pp.2530-2570, 1999. ,
DOI : 10.1200/JCO.1999.17.8.2530
Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial, The Lancet, vol.372, issue.9637, pp.449-56, 20089. ,
DOI : 10.1016/S0140-6736(08)61039-9
Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma, New England Journal of Medicine, vol.356, issue.2, pp.115-139, 2007. ,
DOI : 10.1056/NEJMoa065044
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, Journal of Clinical Oncology, vol.24, issue.1, pp.16-24, 2006. ,
DOI : 10.1200/JCO.2005.02.2574
Recombinant Human Interleukin-2, Recombinant Human Interferon Alfa-2a, or Both in Metastatic Renal-Cell Carcinoma, New England Journal of Medicine, vol.338, issue.18 ,
DOI : 10.1056/NEJM199804303381805
Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial, The Lancet Oncology, vol.12, issue.7, pp.673-80, 2011. ,
DOI : 10.1016/S1470-2045(11)70124-3
Sequential therapy with targeted agents in patients with advanced renal cell carcinoma: Optimizing patient benefit, Cancer Treatment Reviews, vol.38, issue.8 ,
DOI : 10.1016/j.ctrv.2011.12.009
Résistance à la chimiothérapie dans les cancers du rein et perspectives thérapeutiques, Journal d'urologie, vol.101, issue.3, pp.122-126 ,
Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth. Cancer Cell, pp.53-67, 2007. ,
Targeting the PI3K???Akt pathway in kidney cancer, Expert Review of Anticancer Therapy, vol.4, issue.6, pp.863-70, 2007. ,
DOI : 10.1016/S1535-6108(03)00308-8
Phase I Study Combining Treatment with Temsirolimus and Sunitinib Malate in Patients with Advanced Renal Cell Carcinoma, Clinical Genitourinary Cancer, vol.7, issue.1, pp.24-31, 2009. ,
DOI : 10.3816/CGC.2009.n.004
von Hippel-Lindau disease: recent advances and therapeutic perspectives, Expert Review of Anticancer Therapy, vol.98, issue.20, pp.215-248, 2003. ,
DOI : 10.1073/pnas.98.4.1583
Genetics and angiogenesis: the example of von Hippel-Lindau disease]. Bull Cancer, pp.170-179, 2007. ,
Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial, The Lancet, vol.378, issue.9807, pp.1931-1940, 2011. ,
DOI : 10.1016/S0140-6736(11)61613-9
Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206, Journal of Clinical Oncology, vol.26, issue.33, pp.5422-5430, 2008. ,
DOI : 10.1200/JCO.2008.16.9847
Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study, The Lancet Oncology, vol.8, issue.11, pp.975-84, 2007. ,
DOI : 10.1016/S1470-2045(07)70285-1
What is a targeted therapy? The view of the biologist], Bull Cancer, vol.94, issue.7, pp.101-110, 2007. ,
The results of radical nephrectomy for renal cell carcinoma, J ,
1969 mars, pp.297-301 ,
Progress in human tumour immunology and immunotherapy, Nature. mai, vol.17411, issue.6835, pp.380-384, 2001. ,
Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results, Journal of Clinical Oncology, vol.23, issue.24, pp.5474-83, 2005. ,
DOI : 10.1200/JCO.2005.04.192
Sequential Sorafenib and Sunitinib for Renal Cell Carcinoma, The Journal of Urology, vol.182, issue.1, pp.29-34, 2009. ,
DOI : 10.1016/j.juro.2009.02.119
Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma Global ACCR Trial, N Engl J Med Eur. Urol, vol.35655, issue.1, pp.2271-81250, 2007. ,
Brain metastasis from renal cell carcinoma, Cancer, vol.17, issue.S, pp.1641-1649, 2008. ,
DOI : 10.4049/jimmunol.176.3.1456
Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial, Journal of Clinical Oncology, vol.28, issue.6, pp.1061-1069, 2010. ,
DOI : 10.1200/JCO.2009.23.9764
Raf Kinase Inhibitors in Oncology, Oncology Research and Treatment, vol.8, issue.2, pp.101-108, 2005. ,
DOI : 10.1517/eobt.3.2.263.21157
Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer, Nature Genetics, vol.30, issue.4 ,
DOI : 10.1038/ng849
Contrasting Roles of IL-2 and IL-15 in the Life and Death of Lymphocytes Implications for Immunotherapy, Immunity, vol.14, issue.2, pp.105-115, 2001. ,
DOI : 10.1016/S1074-7613(09)00091-0
Aflibercept in the Treatment of Metastatic Colorectal Cancer, Clinical Medicine Insights: Oncology, vol.6, pp.19-30 ,
DOI : 10.4137/CMO.S7432
Immunotherapy for Renal Cell Cancer, Journal of Clinical Oncology, vol.24, issue.35, pp.5576-83, 2006. ,
DOI : 10.1200/JCO.2006.08.3774
A Randomized Trial of Bevacizumab, an Anti???Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer, New England Journal of Medicine, vol.349, issue.5 ,
DOI : 10.1056/NEJMoa021491
BPDE Induced Lymphocytic Chromosome 3p Deletions May Predict Renal Cell Carcinoma Risk, The Journal of Urology, vol.179, issue.6, pp.2416-2437, 2008. ,
DOI : 10.1016/j.juro.2008.01.092
Le concept de cible en cancérologie, John Libbey Eurotext et AMGEN, 2008. ,