Current Status and Future Prospects of Clinically Exploiting Cancer-specific Metabolism-Why Is Tumor Metabolism Not More Extensively Translated into Clinical Targets and Biomarkers?

Magesh Muthu,Anders Nordström

doi:10.3390/ijms20061385

Abstract

Tumor cells exhibit a specialized metabolism supporting their superior ability for rapid proliferation, migration, and apoptotic evasion. It is reasonable to assume that the specific metabolic needs of the tumor cells can offer an array of therapeutic windows as pharmacological disturbance may derail the biochemical mechanisms necessary for maintaining the tumor characteristics, while being less important for normally proliferating cells. In addition, the specialized metabolism may leave a unique metabolic signature which could be used clinically for diagnostic or prognostic purposes. Quantitative global metabolic profiling (metabolomics) has evolved over the last two decades. However, despite the technology’s present ability to measure 1000s of endogenous metabolites in various clinical or biological specimens, there are essentially no examples of metabolomics investigations being translated into actual utility in the cancer clinic. This review investigates the current efforts of using metabolomics as a tool for translation of tumor metabolism into the clinic and further seeks to outline paths for increasing the momentum of using tumor metabolism as a biomarker and drug target opportunity.

Highlights

Tumor cells exhibit a specialized metabolism supporting their superior ability for rapid proliferation, migration, and apoptotic evasion
We do know that ATP synthesis is strongly connected with oxidative phosphorylation, which in turn depends to a large extent on the tricarboxylic acid cycle (TCA) for NADH production [14]
The TCA has several points for anaplerotic/cataplerotic reactions [15,16] and is a focal point for mediating the further metabolic processes required for sustaining the ATP homeostasis: for example, glycolysis, fatty acid synthesis, fatty acid oxidation, and glutaminolysis (α-ketoglutarate)

Summary

Introduction

Tumor cells exhibit a specialized metabolism supporting their superior ability for rapid proliferation, migration, and apoptotic evasion. Identification of specific mechanisms sustaining the global metabolic homeostasis, driven and balanced between by the cancer cells continuous proliferation and their need for maintaining ATP homeostasis, would lead to the identification of therapeutic or biomarker opportunities.

Results

Conclusion