Targeting the Metabolism in Cancer Cells for Cancer Therapy

Abstract

Cellular reactive oxygen species (ROS) are a group of extremely reactive molecules and are produced by metabolic and other reduction-oxidation (redox) reactions from endogenous sources (e.g., mitochondria) or induced by insults from exogenous sources (e.g., anti-cancer drugs, radiation). During redox homeostasis and when ROS level is optimal, ROS perform many vital cellular functions. However, during oxidative stress or dysregulated redox metabolism or anti-oxidant system, and when ROS level is persistently high, ROS induces cellular damage. Notably, ROS-induced oxidative DNA damages, including irreversible genomic mutations or alterations or instability, induce oncogenic transformation of cells and promote carcinogenesis. Interestingly, excess level of ROS can also induce cancer cell apoptosis. Cancer stem cells (CSCs) represent a small population of cells with self-renewal and metastatic characteristics in cancer, and they are sensitive to the level of ROS. Thus, CSCs or non-CSC cancer cells and/or ROS can promote carcinogenesis or cancer growth, metastasis, therapeutic resistance, and relapse. In cancer, CSCs often tend to use aerobic glycolysis that generates lactate, i.e., Warburg effect and non-CSCs use aerobic glycolysis or oxidative phosphorylation (OXPHOS), while normal cells use OXPHOS pathway as their main source for energy production. Recent advances in the field of metabolism, redox system and ROS in cancer cells or CSCs, and their significance in cancer have renewed more interest in targeting the metabolism as a novel strategy for therapy of cancer. In this chapter, we discuss about ROS and their detoxification, and the role of ROS, redox homeostasis, and metabolism in various cancer cells. Furthermore, we also highlight the potential of targeting the metabolism and its redox reactions, and small molecule drugs in inhibiting the cancer cell metabolism.KeywordsReactive oxygen species (ROS)Cancer cellCancer stem cell (CSC)MetabolismReduction-oxidation (redox) reactionGlycolysisWarburg effectTricarboxylicacid (TCA) cycleOxidative phosphorylation (OXPHOS) pathwayCancer therapy