Cancer stem cell metabolism: a potential target for cancer therapy

Abstract

Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to dysregulation in glucose metabolism, fatty acid synthesis, and glutaminolysis. To propagate their lethal effects and maintain survival, tumour cells alter their metabolic requirements to ensure optimal nutrient use for their survival, evasion from host immune attack, and proliferation. It is now evident that cancer cells metabolise glutamine to grow rapidly because it provides the metabolic stimulus for required energy and precursors for synthesis of proteins, lipids, and nucleic acids. It can also regulate the activities of some of the signalling pathways that control the proliferation of cancer cells.This review describes the key metabolic pathways required by CSCs to maintain a survival advantage and highlights how a combined approach of targeting cellular metabolism in conjunction with the use of chemotherapeutic drugs may provide a promising strategy to overcome therapeutic resistance and therefore aid in cancer therapy.

Chromatin Remodeling Factor BRG1 Regulates Stemness and Chemosensitivity of Glioma Initiating Cells

“…Furthermore, BRG1 loss also led to increased expression of Cyclin A2, which interacts with CDK1/2 and promotes G1/S and G2/M cell cycle transition . Taken together our findings strongly suggest that BRG1 plays an important role in restraining GIC proliferation, which may also contribute to GIC drug resistance since chemotherapeutic drugs target proliferating cancer cells . Consistent with the finding that BRG1 loss increased GIC proliferation in vitro, BRG1‐KD GICs injected orthotopically into the brains of mice showed accelerated tumor growth.…”

Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs)

“…The cell killings of the order of >60% in HT-29 WT populations are possibly an indicator of a predominance of non-stem cancer cells/cell populations that are sensitive to high doses of Vitamin C and Niacin. Hence, targeting cancer stem metabolism has been discussed as an effective strategy for cancer therapeutics in the review by Deshmukh et al (2016). Hence, molecular interactions of mutated KRAS protein of HCT-15 cell line and its cellular derivatives (WT, CSC and non-CSC), in response to various doses of Vitamin C and Niacin forms a new future scope of this study.…”

Hypoxia-Inducible Factors and Cancer

“…The precise pathways that confer stemness are still being examined, including JAK/STAT, Wnt/B-catenin, Hedgehog, TGF-beta-Hippo-YAP/TAZ, Notch and Nanog [92–95]. CSCs also exhibit a pronounced shift towards aerobic glycolysis distinct from the remaining tumor bulk [96]. Whether hypoxia promotes stemness, or is simply the milieu in which CSCs exist is not well understood.…”