The metabolic landscape of urological cancers: New therapeutic perspectives

Cancer Lett. 2020 May 1:477:76-87. doi: 10.1016/j.canlet.2020.02.034. Epub 2020 Mar 3.

Abstract

Deregulation of cell metabolism is an established cancer hallmark that contributes to tumor initiation and progression, as well as tumor heterogeneity. In solid tumors, alterations in different metabolic pathways, including glycolysis, pentose phosphate pathway, glutaminolysis and fatty acid metabolism, support the high proliferative rates and macromolecule biosynthesis of cancer cells. Despite advances in therapy, urothelial tumors still exhibit high recurrence and mortality rates, especially in advanced stages of disease. These tumors harbor gene mutations and expression patterns which play an important role in metabolic reprogramming. Taking into account the unique metabolic features underlying carcinogenesis in these cancers, new and promising therapeutic targets based on metabolic alterations must be considered. Furthermore, the combination of metabolic inhibitors with conventional targeted therapies may improve effectiveness of treatments. This review will summarize the metabolic alterations present in urological tumors and the results with metabolic inhibitors currently available.

Keywords: Metabolic inhibitors; Tumor metabolism; Urological tumors.

Publication types

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

MeSH terms

  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism
  • Glucose / metabolism
  • Glutamine / metabolism
  • Humans
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • Lipid Metabolism
  • Male
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Urologic Neoplasms / drug therapy
  • Urologic Neoplasms / metabolism*

Substances

  • Glutamine
  • Glucose