Metabolomic Profiling in Renal Cell Carcinoma Patients: News and Views

SIMPLE SUMMARY: Understanding 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. ABSTRACT: 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.