title: The prospect of precision therapy for renal cell carcinoma.
abstract: The therapeutic landscape of renal cell carcinoma (RCC) has greatly expanded in the last decade. From being a malignancy orphan of effective therapies, kidney cancer has become today a tumor with several treatment options. 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). In this complex scenario it is important to find prognostic and predictive factors that can help in decision making in the treatment of mRCC.
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
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: Pathology Service, Addarii Institute of Oncology, S-Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Heng
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy. Electronic address: fmassari79@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D060890:B7-H1 Antigen / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D005649:Fumarate Hydratase / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D058990:Molecular Targeted Therapy; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D057285:Precision Medicine; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D015398:Signal Transduction; D013385:Succinate Dehydrogenase / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D055372:AMP-Activated Protein Kinases; D060890:B7-H1 Antigen; D004815:Epidermal Growth Factor; D005649:Fumarate Hydratase; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D010982:Platelet-Derived Growth Factor; D061026:Programmed Cell Death 1 Receptor; D051057:Proto-Oncogene Proteins c-akt; D019859:Proto-Oncogene Proteins c-met; D017468:Receptors, Fibroblast Growth Factor; D013385:Succinate Dehydrogenase; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A
keywords: Clear cell renal cell carcinoma; Metastatic renal cell carcinoma; Non-clear cell renal cell carcinoma; PD-1; PD-L1; Personalized medicine; Precision medicine; TKI; Targeted therapy; mTOR