title: Metabolic alterations in renal cell carcinoma.
abstract: Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies.
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy. Electronic address: fmassari79@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Department of Pathology and Diagnostic, A.O.U.I., University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piva
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modena
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bimbatti
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Fantinel
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, AOU Ospedali Riuniti, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D053858:Metabolic Networks and Pathways
keywords: Metabolic pathways; RCC carcinogenesis; Renal cell carcinoma; Therapeutic strategies