Modulating cell differentiation in cancer models

Cancer has been traditionally viewed as a disease characterised by excessive and uncontrolled proliferation, leading to the development of cytotoxic therapies against highly proliferating malignant cells. However, tumours frequently relapse due to the presence of slow-cycling cancer stem cells eluding chemo and radiotherapy. Since these malignant stem cells are largely undifferentiated, inducing their lineage commitment has been proposed as a potential intervention strategy to deplete tumours from their most resistant components. Pro-differentiation approaches have thus far yielded clinical success in the reversion of acute promyelocytic leukaemia (APL), and new developments are fast widening their therapeutic applicability to solid carcinomas. Recent advances in cancer differentiation discussed here highlight the potential and outstanding challenges of differentiation-based approaches.

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Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

Journal of Oncology ◽

10.1155/2011/396076 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 159

Author(s):

Nathan Moore ◽

Stephen Lyle

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Adult Stem Cells ◽

Cell Populations ◽

Proliferative Potential ◽

Cell Cycle Regulators ◽

Slow Cycling ◽

Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

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A 3D Cellular Automaton for Cell Differentiation in a Solid Tumor with Plasticity

Biophysical Reviews and Letters ◽

10.1142/s1793048018500029 ◽

2018 ◽

Vol 13 (01) ◽

pp. 19-28 ◽

Cited By ~ 1

Author(s):

David H. Margarit ◽

Lilia Romanelli ◽

Alejandro J. Fendrik

Keyword(s):

Stem Cells ◽

Cell Differentiation ◽

Cancer Stem Cells ◽

Cellular Automaton ◽

Solid Tumor ◽

Spherical Symmetry ◽

Differentiated Cells ◽

Previous State

A model with spherical symmetry is proposed. We analyze the appropriate parameters of cell differentiation for different kinds of cells (Cancer Stem Cells (CSC) and Differentiated Cells (DC)). The plasticity (capacity to return from a DC to its previous state of CSC) is taken into account. Following this hypothesis, the dissemination of CSCs to another organ is analyzed. The location of the cells in the tumor and the plasticity range for possible metastasis is discussed.

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Metabolic Targeting of Cancer Stem Cells

Frontiers in Oncology ◽

10.3389/fonc.2020.537930 ◽

2020 ◽

Vol 10 ◽

Author(s):

Anna Mukha ◽

Anna Dubrovska

Keyword(s):

Stem Cells ◽

Cell Differentiation ◽

Cancer Stem Cells ◽

Clonal Evolution ◽

Cancer Therapies ◽

Intrinsic Resistance ◽

Anti Cancer ◽

Target Tumor Cell ◽

High Degree ◽

Metabolic Targeting

Most human tumors possess a high heterogeneity resulting from both clonal evolution and cell differentiation program. The process of cell differentiation is initiated from a population of cancer stem cells (CSCs), which are enriched in tumor‐regenerating and tumor‐propagating activities and responsible for tumor maintenance and regrowth after treatment. Intrinsic resistance to conventional therapies, as well as a high degree of phenotypic plasticity, makes CSCs hard-to-target tumor cell population. Reprogramming of CSC metabolic pathways plays an essential role in tumor progression and metastatic spread. Many of these pathways confer cell adaptation to the microenvironmental stresses, including a shortage of nutrients and anti-cancer therapies. A better understanding of CSC metabolic dependences as well as metabolic communication between CSCs and the tumor microenvironment are of utmost importance for efficient cancer treatment. In this mini-review, we discuss the general characteristics of CSC metabolism and potential metabolic targeting of CSC populations as a potent strategy to enhance the efficacy of conventional treatment approaches.

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https://researchopenworld.com/development-of-synthetic-cell-differentiation-agent-formulations-for-the-prevention-and-therapy-of-cancer-via-targeting-of-cancer-stem-cells/#

10.31038/cst.2019412 ◽

2019 ◽

Vol 4 (1) ◽

Keyword(s):

Stem Cells ◽

Cell Differentiation ◽

Cancer Stem Cells ◽

Synthetic Cell ◽

Prevention And Therapy

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A Case of Identity: HOX Genes in Normal and Cancer Stem Cells

Cancers ◽

10.3390/cancers11040512 ◽

2019 ◽

Vol 11 (4) ◽

pp. 512 ◽

Cited By ~ 10

Author(s):

Smith ◽

Zyoud ◽

Allegrucci

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Cancer Stem Cells ◽

Adult Stem Cells ◽

Hox Genes ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Embryonic Stem Cell Differentiation ◽

Hox Gene

Stem cells are undifferentiated cells that have the unique ability to self-renew and differentiate into many different cell types. Their function is controlled by core gene networks whose misregulation can result in aberrant stem cell function and defects of regeneration or neoplasia. HOX genes are master regulators of cell identity and cell fate during embryonic development. They play a crucial role in embryonic stem cell differentiation into specific lineages and their expression is maintained in adult stem cells along differentiation hierarchies. Aberrant HOX gene expression is found in several cancers where they can function as either oncogenes by sustaining cell proliferation or tumor-suppressor genes by controlling cell differentiation. Emerging evidence shows that abnormal expression of HOX genes is involved in the transformation of adult stem cells into cancer stem cells. Cancer stem cells have been identified in most malignancies and proved to be responsible for cancer initiation, recurrence, and metastasis. In this review, we consider the role of HOX genes in normal and cancer stem cells and discuss how the modulation of HOX gene function could lead to the development of novel therapeutic strategies that target cancer stem cells to halt tumor initiation, progression, and resistance to treatment.

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Abstract 3907: Targeting cancer stem cells with microRNA therapeutics and particle radiation in challenging cancer models

10.1158/1538-7445.am2017-3907 ◽

2017 ◽

Author(s):

Guillaume Vares ◽

Yannick Saintigny ◽

Sei Sai ◽

Hirotaka Sugawara ◽

Tetsuo Nakajima

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Particle Radiation ◽

Cancer Models

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Tissue-specific cancer stem cells: reality or a mirage?

Translational Medicine Reports ◽

10.4081/tmr.6535 ◽

2017 ◽

Vol 1 (1) ◽

Cited By ~ 4

Author(s):

Tarik Regad

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Cancer Patients ◽

Targeted Therapies ◽

Cancer Recurrence ◽

Cancer Therapies ◽

Malignant Cells ◽

Significant Progress ◽

Specific Cancer

Equo ne credite, Teucri. Quidquid id est, timeo Danaos et dona ferentes (Do not trust the horse, Trojans! Whatever it is, I fear the Greeks, even bringing gifts) said Laocoön (Virgil, the Aeneid book). Cancer stem cells (CSCs) are populations of cancer cells that can be found in different cancerous tissues and organs, and have properties that are similar to normal stem cells. They are thought to be chemo-resistant and radioresistant and are therefore responsible for cancer recurrence and relapse encountered in cancer patients following chemotherapy and radiotherapy. Although significant progress has been made to characterise CSCs, it is becoming clear that the failure of cancer therapies directed against certain types of aggressive cancers is due to the presence of these malignant cells. Cancer therapies that will rely on a combination of CSCs-targeted therapies, chemotherapy and radiotherapy are more likely to succeed in eradicating aggressive cancers and prevent recurrence in treated patients.

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