The prospect of precision therapy for renal cell carcinoma

Chiara Ciccarese; Matteo Brunelli; Rodolfo Montironi; Michelangelo Fiorentino; Roberto Iacovelli; Daniel Heng; Giampaolo Tortora; Francesco Massari

doi:10.1016/j.ctrv.2016.07.003

The prospect of precision therapy for renal cell carcinoma

Cancer Treat Rev. 2016 Sep:49:37-44. doi: 10.1016/j.ctrv.2016.07.003. Epub 2016 Jul 12.

Authors

Chiara Ciccarese¹, Matteo Brunelli², Rodolfo Montironi³, Michelangelo Fiorentino⁴, Roberto Iacovelli¹, Daniel Heng⁵, Giampaolo Tortora¹, Francesco Massari⁶

Affiliations

¹ Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
² Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata (AOUI), University of Verona, Verona, Italy.
³ Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, AOU Ospedali Riuniti, Ancona, Italy.
⁴ Pathology Service, Addarii Institute of Oncology, S-Orsola-Malpighi Hospital, Bologna, Italy.
⁵ Department of Medical Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
⁶ Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy. Electronic address: [email protected].

PMID: 27453294
DOI: 10.1016/j.ctrv.2016.07.003

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.

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.

Publication types

Review

MeSH terms

AMP-Activated Protein Kinases / metabolism
B7-H1 Antigen / genetics
Carcinoma, Renal Cell / drug therapy*
Carcinoma, Renal Cell / genetics
Carcinoma, Renal Cell / metabolism
Epidermal Growth Factor / metabolism
Fumarate Hydratase / metabolism
Glucose Transporter Type 1 / metabolism
Glucose Transporter Type 4 / metabolism
Hepatocyte Growth Factor / genetics
Hepatocyte Growth Factor / metabolism
Humans
Kidney Neoplasms / drug therapy*
Kidney Neoplasms / genetics
Kidney Neoplasms / metabolism
Metabolic Networks and Pathways
Molecular Targeted Therapy
Mutation
Phosphatidylinositol 3-Kinases / metabolism
Platelet-Derived Growth Factor / metabolism
Precision Medicine
Programmed Cell Death 1 Receptor / genetics
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins c-met / genetics
Receptors, Fibroblast Growth Factor / genetics
Signal Transduction
Succinate Dehydrogenase / metabolism
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism
Vascular Endothelial Growth Factor A / metabolism

Substances

B7-H1 Antigen
Glucose Transporter Type 1
Glucose Transporter Type 4
Platelet-Derived Growth Factor
Programmed Cell Death 1 Receptor
Receptors, Fibroblast Growth Factor
Vascular Endothelial Growth Factor A
Epidermal Growth Factor
Hepatocyte Growth Factor
Succinate Dehydrogenase
Proto-Oncogene Proteins c-met
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
AMP-Activated Protein Kinases
Fumarate Hydratase