[Signalling pathways in renal-cell carcinoma: from the molecular biology to the future therapy].
The medical treatment of renal-cell carcinoma, and of its most frequent subtype, clear cell renal-cell carcinoma, has recently been drastically changed by the emergence of targeted therapies. The development of these drugs has been made possible by more precise knowledge of molecular mechanisms involved in the carcinogenesis of these tumors. We present in this article the molecular pathways linked to targeted therapies for clear cell renal-cell carcinoma: VHL/HIF/VEHF and PI3K/AkT/mTOR pathways. We also describe succinctly the EGFR pathways, and the molecular mechanisms involved in other histological subtypes. Then, we briefly describe how these targeted therapies work. We finally discuss how biology could improve the use of these therapies, by developing new prognostic factors, and predictive factors of response to treatment.
Edeline
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Service d'anatomie et de cytologie pathologique, pôle cellules et tissus, CHU de Pontchaillou 35033 Rennes cedex 09, France.
Vigneau
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C
Patard
J-J
JJ
Rioux-Leclercq
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D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D018832:Molecular Chaperones; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D066246:ErbB Receptors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; C476078:FLCN protein, human; C497442:HIF1A protein, human; C108825:VBP1 protein, human; C546842:MTOR protein, human; C512478:EGFR protein, human