CSCs are known to be extremely chemoresistant, and in recent times, they have piqued the interest of researchers as crucial tumour-initiating cells that may also be involved in tumour recurrence after chemotherapy. Cancer cells have the ability to change their metabolism in order to meet bio-energetic and biosynthetic needs. They rely heavily on aerobic glycolysis for energy production and are related to higher fatty acid synthesis and glutamine utilisation rates.
Many preclinical and clinical investigations have revealed that some CSC populations have intrinsic and extrinsic pathways that provide them with higher radioresistance and chemoresistance than the majority of tumour cells. The efficient DNA repair, low proliferative rate, protective tumour microenvironment, regulation of cellular redox homeostasis, and immune evasion all contribute to CSCs’ relatively high therapeutic resistance. CSCs’ modified metabolism contributes significantly to their treatment resistance. A thorough understanding of CSC metabolic properties and their molecular basis will aid in the development of novel therapeutic techniques that precisely target CSCs and increase cancer control efficiency.
Metabolic Features of Cancer Stem Cells
Glycolysis is a key and well-studied metabolic feature of cancer cells. Rapidly tissues, such as cancerous tumours, require more energy. Energy in the form of adenosine triphosphate (ATP) is produced in differentiated cells through oxidative phosphorylation (OXPHOS) in mitochondria. For instance, glycolysis is the major characteristic of various cancer cells including breast cancer, hepatocellular carcinoma, lung cancer; OXPHOS in ovary cancer, lung cancer and pancreatic cancer.
The Metabolic Interaction between CSCs with Tumor Microenvironment
The interaction of the tumour microenvironment with cancer stem cells can help CSC survival and phenotype. Cancer-associated fibroblasts, endothelial cells, immune cells, and extracellular matrix make up the tumour microenvironment. Hypoxia is one of several crucial elements for the maintenance of CSC metabolism. Hypoxia is a significant feature of the tumour microenvironment, and it plays an important role in CSC maintenance, quiescence, and therapeutic resistance.
The Outlook
Tumour metabolism is of critical clinical importance since it drives tumour resistance to standard anticancer drugs, and metabolic co-targeting appears as a fresh, very promising notion for improving the efficacy of current treatment techniques. CSCs are responsible for tumour maintenance and regrowth following treatment, hence metabolic suppression of tumour development by targeting them is of particular interest. The limitations of current CSC tests, as well as the absence of experimental models that depict complex tumour microenvironments, pose a significant hurdle to the development of metabolic CSC-targeting techniques and their clinical translation.
The intratumoral variability of CSC metabolic properties, as well as the considerable adaptability of CSC nutritional needs during tumour growth and treatment, poses multiple hazards. Future research on heterogeneous CSC metabolic states at the single-cell level, as well as the use of advanced computational tools to combine multi-omics data, may provide insights for the creation of innovative metabolic targeting methodologies and their incorporation into current therapy regimens.
