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Eradicating Cancer Stem Cells: Concepts, Issues, and Challenges

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Opinion statement:

The cells of malignant cancers result in the evolution of cells with stem-like characteristics, commonly known as cancer stem cells (CSCs). Progress of anticancer therapies is severely hampered because of disease relapse mostly in a more aggressive form due to CSCs. These CSCs are more or less like embryonic or tissue stem cells, known for their capacity of self-renewal, exactly recapitulate of the original tumor. Deregulation of key stem cell pathways like Wnt, Hedgehog (Hh), and Notch is attributed towards the rise of CSCs. Recent breakthroughs offer better insights into CSC signaling. Scientists have developed several combinatorial therapies like targeting one/multiple of these CSC pathways. The article summarized various markers used to identify CSCs and discuss major signaling pathways in them. The futuristic probabilities to use CSC therapeutics in clinical development have been discussed. Our views have been highlighted on the future directions for targeting advances in the clinical development.

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Abbreviations

ABC:

ATP-binding cassette

ALDH1:

aldehyde dehydrogenase 1

APC:

adenomatous polyposis coli

BCC:

basal cell carcinoma

Bmi 1:

B cell-specific Moloney murine leukemia virus integration site 1

BrdU:

bromodeoxyuridine

BTSC:

brain tumor stem cell

CBC:

Crypt base columnar

CCL5:

Chemokine C-C motif ligand 5

CCR5:

Chemokine C-C Motif Receptor 5

CKIε:

Casein Kinase Iε

CSCs:

Cancer stem cells

CXCL12:

C-X-C motif chemokine ligand 12

CXCR4:

Chemokine receptor type 4

DKK1:

Dickkopf related protein 1

DLL:

Delta-like ligands

EMT:

Epithelial-to-mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

ES cells:

Embryonic stem cells

ESA:

Epithelial surface antigen

FGF20:

Fibroblast growth factor 20

GBM:

Glioblastomas

GCG:

Glucagon

GI:

Gastrointestinal

GPI-AP:

Glycosylphosphatidylinositol-anchored protein

GSI:

Gamma secretase inhibitors

Hh:

Hedgehog

HpSCs:

Hepatocellular stem cells

HSPCs:

Hepatic stem/progenitor cells

ICD:

Intracellular domain

IWR compounds:

Inhibitors of Wnt response compounds

JAG1 and JAG2:

Jagged proteins

MB:

Medullo-blastoma

MSCs:

Mesenchymal stem cells

NDRG2:

N myc downregulated gene 2

NICD:

Notch intracellular domain

NLK:

Nemo-like kinase

NOD-SCID:

Non-obese diabetic- severe combined immunodeficient

PPARγ:

Peroxisome proliferator-activated receptor γ

SCFR:

Stem cell factor receptor

SDF-1:

Stromal cell-derived factor

SHh:

Secreted Hedgehog ligands

Shh:

Sonic Hedgehog

SMO:

Small molecule anti-smoothened

SP:

Side population

TACE:

Tumor, necrosis factor alpha-converting enzyme

TCF:

T cell factor

WISP1:

WNT1- inducible signaling pathway

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Acknowledgements

All the authors thank the Vice-Chancellor of CUPB for the support.

Funding

The work was supported by CUPB-RSM and UGC startup grants.

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Authors and Affiliations

  1. Department of Environmental Science and Technology, Central University of Punjab, Bathinda, Punjab, 151001, India

    Gurpreet Kaur MPhil

  2. Laboratory of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Mansa Road, Bathinda, Punjab, 151001, India

    Praveen Sharma MSc & Sandeep Singh PhD

  3. Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India

    Nilambra Dogra PhD

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  1. Gurpreet Kaur MPhil
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  2. Praveen Sharma MSc
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  3. Nilambra Dogra PhD
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  4. Sandeep Singh PhD
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Correspondence to Sandeep Singh PhD.

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Gurpreet Kaur, Praveen Sharma, Nilambra Dogra, and Sandeep Singh declare they have no conflict of interest.

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Kaur, G., Sharma, P., Dogra, N. et al. Eradicating Cancer Stem Cells: Concepts, Issues, and Challenges. Curr. Treat. Options in Oncol. 19, 20 (2018). https://doi.org/10.1007/s11864-018-0533-1

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