Metabolic alterations in renal cell carcinoma

Francesco Massari; Chiara Ciccarese; Matteo Santoni; Matteo Brunelli; Francesco Piva; Alessandra Modena; Davide Bimbatti; Emanuela Fantinel; Daniele Santini; Liang Cheng; Stefano Cascinu; Rodolfo Montironi; Giampaolo Tortora

doi:10.1016/j.ctrv.2015.07.002

Metabolic alterations in renal cell carcinoma

Cancer Treat Rev. 2015 Nov;41(9):767-76. doi: 10.1016/j.ctrv.2015.07.002. Epub 2015 Jul 9.

Affiliations

¹ Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy. Electronic address: fmassari79@gmail.com.
² Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
³ Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy.
⁴ Department of Pathology and Diagnostic, A.O.U.I., University of Verona, Verona, Italy.
⁵ Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, Italy.
⁶ Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.
⁷ Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, United States.
⁸ Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, AOU Ospedali Riuniti, Ancona, Italy.

PMID: 26169313
DOI: 10.1016/j.ctrv.2015.07.002

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.

Keywords: Metabolic pathways; RCC carcinogenesis; Renal cell carcinoma; Therapeutic strategies.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Carcinoma, Renal Cell / metabolism*
Humans
Kidney Neoplasms / metabolism*
Metabolic Networks and Pathways