title: From development to cancer: lessons from the kidney to uncover new therapeutic targets.
abstract: Several genes play essential roles in human development and alteration of their expression or regulation leads to various pathologies. This review examines the literature on the expression and the roles of neurogenic locus notch homolog protein (NOTCH), sonic Hedgehog (SHH) and wingless-type (WNT) pathways, as well as the nephrogenic transcription factors Wilms' tumor 1 (WT1), paired box 2 (PAX2) and homeobox protein lim-1 (LIM1) in clear cell renal cell carcinoma. Besides being re-expressed in human tumors, the inhibition of these factors has strong antitumor activity both in vitro and in vivo. Interestingly, these pathways are also part of the molecular network involved in the development of organs including nephrogenesis. The identification of developmental pathways involved in clear cell renal cell carcinoma growth places an additional piece into the molecular puzzle of cancer mechanisms. Moreover, the evaluation of these molecules could pave the way to innovative and safe therapies for this refractory disease. Valuable prognostic markers might also be identified through these studies. Finally, the proof of concept in other types of cancer is reviewed.
authors.affiliation: INSERM U682, Section of Renal Cancer and Renal Physiopathology, School of Medicine, University of Strasbourg, Strasbourg, France. valerian.dormoy@unistra.fr
authors.forename: Valérian
authors.initials: V
authors.lastname: Dormoy
authors.forename: Didier
authors.initials: D
authors.lastname: Jacqmin
authors.forename: Hervé
authors.initials: H
authors.lastname: Lang
authors.forename: Thierry
authors.initials: T
authors.lastname: Massfelder
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D058990:Molecular Targeted Therapy; D051762:PAX2 Transcription Factor / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D025721:WT1 Proteins / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D060850:LIM-Homeodomain Proteins; D051762:PAX2 Transcription Factor; D051880:Receptors, Notch; D025721:WT1 Proteins; D051153:Wnt Proteins