Metabolomic Profiling in Renal Cell Carcinoma Patients: News and Views.

Gaetano Aurilio,Rodolfo Montironi,Elena Verri,Nicola Battelli,Alessandro Rizzo,Alessia Cimadamore,Matteo Santoni,Francesco Massari,Veronica Mollica

doi:10.3390/cancers13205229

Abstract

Simple SummaryUnderstanding the metabolic basis of renal cell carcinoma (RCC) has been of paramount importance in defining therapeutic management in clinical practice. Unfortunately, cancer drug resistance continues to be a major cause of treatment failure. Accordingly, developing new treatment perspectives targeting new metabolisms can contribute to overcoming the development of multidrug resistance, and thus optimize patient cure. In this review, we will define and discuss the outline of RCC metabolism, and we will describe certain therapeutic strategies targeting metabolic pathways. The PI3K/Akt signaling pathway continues to be the main target of clinical investigation in RCC patients. Data from metabolic pathways such as c-Met, GSH, and HDAC, variously targeted in combination with PI3K/Akt inhibitors, seem to offer new potential treatment opportunities for the research community. In this view, further studies are warranted.Background: We address novelty regarding metabolomic profiling in renal cell carcinoma (RCC) patients, in an attempt to postulate potential treatment strategies. Methods: A large-scale literature search in existing scientific websites focusing on the keywords “renal cell carcinoma”, “clear cell histology”, “papillary histology”, “metabolomic profiling”, and “therapeutics” was performed. Results: The PI3K/Akt signaling pathway is key in clear cell RCC metabolism and accordingly several drugs are presently available for routine use in clinical practice. Along this line, new treatment combinations against PI3K/Akt family members are currently under clinical investigation. On the other hand, new developed targets such as c-Met tyrosine kinase domain, glutathione (GSH) metabolism, and histone deacetylases enzymes (HDAC), as well as therapeutic strategies targeting them are currently being tested in clinical trials and here discussed. Conclusions: In RCC patients, the PI3K/Akt signaling is still the most effective targetable pathway. Targeting other metabolic pathways such as c-Met, GSH, and HDAC appears to be a promising approach and deserve further insights.

Highlights

We address novelty regarding metabolomic profiling in renal cell carcinoma (RCC) patients, in an attempt to postulate potential treatment strategies
The phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway is key in clear cell RCC metabolism and several drugs are presently available for routine use in clinical practice
Several therapeutic strategies targeting different metabolic pathways in RCC have been developed in the last decades

Summary

Introduction

Results: The PI3K/Akt signaling pathway is key in clear cell RCC metabolism and several drugs are presently available for routine use in clinical practice. Along this line, new treatment combinations against PI3K/Akt family members are currently under clinical investigation. Data on cancer cell metabolism have shown that cancer cells are prone to a metabolic energy reprogramming for supporting cell growth and division, and such metabolism reprogramming has been listed as one of the cornerstones of cancer development [3] Along this line, the Warburg effect—otherwise known as aerobic glycolysis—is one of the first metabolic alterations to be detected, and is present in the majority of cancer cells. Epigenetic mechanisms have been recognized for deregulating certain metabolic processes implicated in growth and cell survival of RCC [6]

Objectives

Findings

Discussion

Conclusion