Published online Jun 26, 2020. doi: 10.4252/wjsc.v12.i6.448
Peer-review started: February 24, 2020
First decision: April 25, 2020
Revised: May 9, 2020
Accepted: May 19, 2020
Article in press: May 19, 2020
Published online: June 26, 2020
Normal cells mainly rely on oxidative phosphorylation as an effective energy source in the presence of oxygen. In contrast, most cancer cells use less efficient glycolysis to produce ATP and essential biomolecules. Cancer cells gain the characteristics of metabolic adaptation by reprogramming their metabolic mechanisms to meet the needs of rapid tumor growth. A subset of cancer cells with stem characteristics and the ability to regenerate exist throughout the tumor and are therefore called cancer stem cells (CSCs). New evidence indicates that CSCs have different metabolic phenotypes compared with differentiated cancer cells. CSCs can dynamically transform their metabolic state to favor glycolysis or oxidative metabolism. The mechanism of the metabolic plasticity of CSCs has not been fully elucidated, and existing evidence indicates that the metabolic phenotype of cancer cells is closely related to the tumor microenvironment. Targeting CSC metabolism may provide new and effective methods for the treatment of tumors. In this review, we summarize the metabolic characteristics of cancer cells and CSCs and the mechanisms of the metabolic interplay between the tumor microenvironment and CSCs, and discuss the clinical implications of targeting CSC metabolism.
Core tip: Accumulating evidence indicates that the inadequacy of many treatments is due to their failure to target cancer stem cells (CSCs). Therefore, CSCs are a promising target for cancer treatment. Recently, it has been reported that CSCs exhibit a unique metabolic phenotype compared to normal cancer cells (non-CSCs), and CSCs can dynamically transform their metabolic state to favor glycolysis or oxidative metabolism. However, the mechanism of the metabolic plasticity of CSCs has not been fully elucidated, and existing evidence indicates that the metabolic phenotype of cancer cells is closely related to the tumor microenvironment (TME). In this article, we summarize the metabolic characteristics of non-CSCs and CSCs, highlight the mechanisms by which CSCs alter their energy metabolism via interactions with the surrounding TME, and discuss the potential therapeutic strategies to target energy metabolism in CSCs.