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Potential Therapies Targeting Metabolic Pathways in Cancer Stem Cells
Yao-An Shen1,2,3, Chang-Cyuan Chen1, Bo-Jung Chen4
1Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Abstract:
Cancer stem cells (CSCs) are heterogeneous cells with stem cell-like properties that are responsible for therapeutic resistance, recurrence, and metastasis, and are the major cause for cancer treatment failure. Since CSCs have distinct metabolic characteristics that plays an important role in cancer development and progression, targeting metabolic pathways of CSCs appears to be a promising therapeutic approach for cancer treatment. Here we classify and discuss the unique metabolisms that CSCs rely on for energy production and survival, including mitochondrial respiration, glycolysis, glutaminolysis, and fatty acid metabolism. Because of metabolic plasticity, CSCs can switch between these metabolisms to acquire energy for tumor progression in different microenvironments compare to the rest of tumor bulk. Thus, we highlight the specific conditions and factors that promote or suppress CSCs properties to portray distinct metabolic phenotypes that attribute to CSCs in common cancers. Identification and characterization of the features in these metabolisms can offer new anticancer opportunities and improve the prognosis of cancer. However, the therapeutic window of metabolic inhibitors used alone or in combination may be rather narrow due to cytotoxicity to normal cells. In this review, we present current findings of potential targets in these four metabolic pathways for the development of more effective and alternative strategies to eradicate CSCs and treat cancer more effectively in the future.
Insights
Cancer stem cells (CSCs) possess unique metabolic pathways crucial for tumor growth and treatment resistance. Targeting these cancer stem cell metabolisms offers a promising strategy for developing novel cancer therapies.
Area of Science:
- Oncology
- Cancer Metabolism
- Cellular Biology
Background:
- Cancer stem cells (CSCs) drive therapeutic resistance, recurrence, metastasis, and treatment failure.
- CSCs exhibit distinct metabolic characteristics vital for cancer development and progression.
- Targeting CSC metabolism presents a promising therapeutic avenue for cancer treatment.
Purpose of the Study:
- To classify and discuss the unique metabolic pathways utilized by CSCs for energy and survival.
- To highlight metabolic plasticity and environmental factors influencing CSC phenotypes.
- To identify potential therapeutic targets within CSC metabolic pathways.
Main Methods:
- Review and classification of CSC metabolic pathways: mitochondrial respiration, glycolysis, glutaminolysis, and fatty acid metabolism.
- Analysis of metabolic plasticity and environmental influences on CSCs.
- Identification of factors promoting or suppressing CSC properties and metabolic phenotypes.
Main Results:
- CSCs rely on distinct metabolic pathways including mitochondrial respiration, glycolysis, glutaminolysis, and fatty acid metabolism.
- Metabolic plasticity allows CSCs to adapt and acquire energy in diverse microenvironments.
- Specific conditions and factors modulate CSC metabolic phenotypes in common cancers.
Conclusions:
- Understanding CSC metabolism provides new anticancer opportunities and can improve patient prognosis.
- Targeting CSC metabolic pathways offers potential for developing more effective cancer eradication strategies.
- Further research is needed to optimize therapeutic strategies due to potential cytotoxicity of metabolic inhibitors.
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