Cancer stem cell metabolism

Peiris-Pagès, Maria; Martinez‐Outschoorn, Ubaldo; Pestell, Richard G.; Sotgia, Federica; Lisanti, Michael P.

doi:10.1186/s13058-016-0712-6

Cited by 387 publications

(368 citation statements)

References 97 publications

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“…Although much is known regarding metabolic pathways important for tumour survival, the potential for therapeutic metabolic alteration of CSCs still remains under investigation [35, 36]. Recent studies indicate that CSCs have different metabolic properties when compared to the tumour bulk.…”

Section: Cscs and Their Metabolic Alterationsmentioning

confidence: 99%

Cancer stem cell metabolism: a potential target for cancer therapy

2016

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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.

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Section: Cscs and Their Metabolic Alterationsmentioning

confidence: 99%

Cancer stem cell metabolism: a potential target for cancer therapy

2016

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“…[64] In contrast, other studies on pancreatic and other breast cancer cell lines reported increased mitochondrial respiration in the CSC population. [65] This may be linked to CSCs rewiring their metabolic states depending on the surrounding cellular environment. Furthermore, different types of tumors may contain CSCs exhibiting different underlying metabolic features.…”

Section: Targeting the Metabolic State Of Cscs: Mitochondrial Metabolmentioning

confidence: 99%

Targeting Cancer Stem Cells with Small Molecules

Müller

Cañeque

Acevedo

et al. 2017

Israel Journal of Chemistry

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Cancers arise as a result of physiological imbalances and subsequent uncontrolled cell division. Cancer initiation requires a set of biochemical alterations, including some occurring at the genetic and epigenetic levels. Thus, tumors are heterogeneous in nature making it challenging to selectively target different cancer cells by means of small molecule intervention. The paradigm of cancer stem cells (CSCs) describes subpopulations of cells with high selfrenewal and tumor-seeding capacity. These cells, typically refractory to conventional therapies, can give rise to relapse after treatment. Combinatorial strategies, including drugs that selectively target this population of cells, have emerged in recent years. Here, we review how discovery-basedunbiased -screening approaches [1] have helped identify small molecules that specifically target CSCs. We also highlight biological pathways characteristic of CSCs that can potentially be selectively targeted in a hypothesis-driven manner by small molecules. We describe molecules that effectively target CSCs and emphasize what is known about their biological modes of action. The diversity and complexity of biochemical processes that CSCs may be addicted to, raises the question of how selective targeting of these pathways can be achieved. This challenge may be addressed by the continuing production of structurally complex and diverse small molecules using target and diversity-oriented synthesis approaches.[2]

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“…To functionally enrich for CSCs, the entire cell population can be trypsinized and seeded as a single-cell suspension onto low-attachment plates [1,2]. Under these conditions, the majority of “bulk” cancer cells die (> 90%) via apoptosis, while only the CSCs survive and propagate, ultimately resulting after 5 d in the formation of 3D spheroid structures.…”

Section: Mitochondrial Function Is Required For Csc Propagationmentioning

confidence: 99%

A mitochondrial based oncology platform for targeting cancer stem cells (CSCs): MITO-ONC-RX

et al. 2018

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Here, we wish to propose a new systematic approach to cancer therapy, based on the targeting of mitochondrial metabolism, especially in cancer stem cells (CSCs). In the future, we envision that anti-mitochondrial therapy would ultimately be practiced as an add-on to more conventional therapy, largely for the prevention of tumor recurrence and cancer metastasis. This mitochondrial based oncology platform would require a panel of FDA-approved therapeutics (e.g. Doxycycline) that can safely be used to inhibit mitochondrial OXPHOS and/or biogenesis in CSCs. In addition, new therapeutics that target mitochondria could also be developed, to optimize their ability to eradicate CSCs. Finally, in this context, mitochondrial-based biomarkers (i.e. “Mito-signatures”) could be utilized as companion diagnostics, to identify high-risk cancer patients at diagnosis, facilitating the early detection of tumor recurrence and the prevention of treatment failure. In summary, we suggest that new clinical trials are warranted to test and possibly implement this emerging treatment strategy, in a variety of human cancer types. This general approach, using FDA-approved antibiotics to target mitochondria, was effective in killing CSCs originating from many different cancer types, including DCIS, breast (ER(+) and ER(-)), prostate, ovarian, lung and pancreatic cancers, as well as melanoma and glioblastoma, among others. Thus, we propose the term MITO-ONC-RX, to describe this anti-mitochondrial platform for targeting CSCs. The use of re-purposed FDA-approved drugs will undoubtedly help to accelerate the clinical evaluation of this approach, as these drugs can move directly into Phase II clinical trials, saving considerable amounts of time (10–15 y) and billions in financial resources.

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Cancer stem cell metabolism

Cited by 387 publications

References 97 publications

Cancer stem cell metabolism: a potential target for cancer therapy

Cancer stem cell metabolism: a potential target for cancer therapy

Targeting Cancer Stem Cells with Small Molecules

A mitochondrial based oncology platform for targeting cancer stem cells (CSCs): MITO-ONC-RX

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