This document discusses cancer stem cells (CSCs) and new therapeutic approaches to target them. It introduces CSCs, their characteristics like self-renewal and chemoresistance. CSCs can be identified by specific cell surface markers and sphere formation assays. New therapies aim to target CSCs' signaling pathways, surface markers, drug efflux pumps, and microenvironment. Targeting CSCs provides a promising approach for improving cancer treatment outcomes as CSCs are responsible for tumor growth, metastasis, and therapeutic resistance.

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Cancer Stem Cells &
New Therapeutic approach
Supervisor:
Dr Khirollah
Dr Rashidi

3.  Introduction
 History of CSCs
 Characteristics of CSCs
 CSCs Specific Markers
 The cause of resistance to chemotherapy
 New Therapies to Target Cancer Stem Cells
 CSCs Specific Markers Therapy
 Targeting Signal Pathways
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Outlines

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Cancer Stem Cells

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* Atena, M., Reza, A.M. and Mehran, G. (2014) A Review on the Biology of Cancer Stem Cells. Stem Cell
Discovery, 4, 83-89
Origin Of CSCs

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Somatic stem cell
Self-renew
highly regulate differentiate
produces mature tissue
Migrate to distant tissues
Long lifespan
Resistant to apoptosis
Cancer stem cell
Self-renew
poorly regulated differentiate
produces tumor
Metastasize to distant sites
Long lifespan
Resistant to apoptosis

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1868 — The term “stem cell” appears in scientific literature, in German
 biologist Ernst Haeckel uses the phrase stem cell to describe the fertilized egg
that becomes an organism
June 1, 1909 — Russian academic Alexander Maxi mow lectures at the Berlin
 Hematological Society on a theory that all blood cells come from the same
ancestor cell
1978: Stem cells were discovered in human cord blood
1981: First in vitro stem cell line developed from mice
 1988: Embryonic stem cell lines created from a hamster
 1995: First embryonic stem cell line derived from a primate
1997: Cloned lamb from stem cells
 1997: Leukemia origin found as hematopoietic stem cell, indicating possible
proof of cancer stem cells
HISTORY OF CSCs

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* Self-renewal and differentiation
*Small number in cancer cells
* Chemo resistance
* Resistance to radiation therapy
* Stay in the resting phase of the cell cycle
* High metastatic ability
* Sphere forming ability
* Expression of cancer stem cell markers
* High ABC transporter expression
Toshiyuki Ishiwata, Review Article, Cancer stem cells and epithelial-
mesenchymal transition: Novel therapeutic targets for cancer,2016
Characters Of CSCs

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*Sphere formation (Ultra low attachment plate)
* Fluorescence-activated cell sorting technique
* magnetic-activated cell sorting technique
Identification of CSCs

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13. Fluorescence-activated cell sorting technique
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15. Cancer Stem Cell Markers
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16. mechanisms leading to cancer stem cell resistance
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17. Chen K et al, Act Pharma Sinica 2013
Therapies targeting cancer stem cells
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*The Hedgehog signaling pathway
*The Notch signaling pathway
*The Wnt signaling pathway
Targeting the molecular signaling pathways

19. The Hedgehog signaling pathway
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The Hedgehog signaling pathway

21. The Notch signaling pathway
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The Wnt signaling pathway

23. Update On Clinical Trials For CSC Mole Targets
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*CD133 in hepatocellular and gastric cancer
*CD44+ CD24+ in pancreatic CSCs
*CD9+ CD24+ CD26+in human malignant mesothelioma CSCs
*Among these markers, CD133 is considered the most important
CSC-associated marker identified so far
Targeting surface markers

25. Targeting drug-detoxify enzymes
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26. Targeting drug-efflux pumps
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27. Targeting microenvironment CSC
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AMO

29. Manipulation of miRNA expression
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30. Induction of CSCs apoptosis
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31. Induction of CSC differentiations
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suberoylanilide hydroxamic acid
(SAHA), ATRA

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* CSCs are responsible not only for tumor initiation, development, and metastasis, but also for
therapeutic resistance.
* These traditional approaches usually include systemic or local toxicity.
* new treatments targeting CSCs are necessary for improving patient survival rate and elongating life
span.
* These targeting strategies provide novel and promising approaches for CSC-targeted cancer therapy.
* the combination of targeted therapies directly eliminate.
* Since CSCs and normal stem cells share many properties, targeting CSCs may unfortunately affect
normal stem cells.
* more precise targeting therapies which can selectively target CSCs but spare normal stem cells are
greatly needed
Conclusion and perspectives

33. References
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*1.Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic
implications. Annual Review of Pathology: Mechanisms of Disease. 2016;11:47-76.
2.Han L, Shi S, Gong T, Zhang Z, Sun X. Cancer stem cells: therapeutic
implications and perspectives in cancer therapy. Acta Pharmaceutica Sinica B.
2013;3(2):65-75.
3.Papaccio F, Paino F, Regad T, Papaccio G, Desiderio V, Tirino V. Concise
Review: Cancer Cells, Cancer Stem Cells, and Mesenchymal Stem Cells: Influence
in Cancer Development. Stem cells translational medicine. 2017;6(12):2115-25.
4.Lau EY-T, Ho NP-Y, Lee TK-W. Cancer stem cells and their
microenvironment: biology and therapeutic implications. Stem cells international.
2017;2017.
5.Deshmukh A, Deshpande K, Arfuso F, Newsholme P, Dharmarajan A. Cancer
stem cell metabolism: a potential target for cancer therapy. Molecular cancer.
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6.Hu Y, Fu L. Targeting cancer stem cells: a new therapy to cure cancer
patients. American journal of cancer research. 2012;2(3):340.
7.Tume L, Paco K, Ubidia-Incio R, Moya J. CD133 in breast cancer cells and in
breast cancer stem cells as another target for immunotherapy. Gaceta Mexicana de
Oncología. 2016;15(1):22-307.

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