1. Mohammed Charbat

2. CONTENTS
CONCEPT OF CANCER STEM CELLS
HISTORY
ORIGIN OF CANCER STEM CELLS
ISOLATION AND MARKERS
ROLE OF CANCER STEM CELLS IN CANCER METASTASIS
ROLE OF CANCER STEM CELLS IN DRUG RESISTANCE
THERAPUITIC APPLICATIONS

3. Definition
CSC is a general term referring to the cancer cells capable of differentiation and self-renewal which is the role of CSCs chemotherapy resistance.

4. Cancer is like a tissue (Heterogeneous Cells)
Many tumors seem likewise to consist of cells in varied states of differentiation, with different capacities for cell division and self-renewal.

6. CONTENTS CONCEPT OF CANCER STEM CELLS HISTORY
ORIGIN OF CANCER STEM CELLS
ISOLATION AND MARKERS
ROLE OF CANCER STEM CELLS IN CANCER METASTASIS
ROLE OF CANCER STEM CELLS IN DRUG RESISTANCE
THERAPUITIC APPLICATIONS

7. History
In 1855, German pathologist stated that cancers arise from the activation of dormant, embryonic- like cells present in mature tissue and argued that cancer does not simply appear spontaneously.
150 years later, Lapidot and colleagues came up with the CSC hypothesis

8. A small chance only 1% that a cancer cell chosen at random and transplanted to an immunodeficient mouse can produce a new tumor

9. This doesn’t prove that cancer cells are heterogeneous since it is possible that only 1% of cells transplanted could found a suitable environment for tumor growth

10. However, when monoclonal antibodies where used to isolate cancer cells resembling stem cells of the tissue of origin of that cancer, these cells were found to have a significantly enhanced ability to generate new tumors.

11. CONTENTS
1- CONCEPT OF CANCER STEM CELLS 2- HISTORY 3- ORIGIN OF CANCER STEM CELLS 4- ISOLATION AND MARKERS 5- ROLE OF CANCER STEM CELLS IN CANCER METASTASIS 6- ROLE OF CANCER STEM CELLS IN DRUG RESISTANCE 7- THERAPUITIC APPLICATIONS

12. Origin

13. So is it the initial cell ?
What is TPC
(Tumor Propagating Cell) ?

14. CONTENTS 1- CONCEPT OF CANCER STEM CELLS 2- HISTORY
3- ORIGIN OF CANCER STEM CELLS
4- ISOLATION AND MARKERS
5- ROLE OF CANCER STEM CELLS IN CANCER METASTASIS
6- ROLE OF CANCER STEM CELLS IN DRUG RESISTANCE
7- THERAPUITIC APPLICATIONS

16. FACS: fluorescent activated cell sorting

17. MACS: MAGNATIC CELL SORTING

18. Especial cell markers are known for the stem cells in several types of cancers

19. CONTENTS 1- CONCEPT OF CANCER STEM CELLS 2- HISTORY
3- ORIGIN OF CANCER STEM CELLS
4- ISOLATION AND MARKERS
5- ROLE OF CANCER STEM CELLS IN CANCER METASTASIS
6- ROLE OF CANCER STEM CELLS IN DRUG RESISTANCE
7- THERAPUITIC APPLICATIONS

20. ROLE OF CANCER STEM CELLS IN INITIATION AND METASTASIS
Their role in tumor initiation and propagation has already been confirmed
Their role in metastasis still needs more research

21. CANCER STEM CELLS SHARE SOME FEATURES WITH NORMAL STEM CELLS
Dormancy
Activation of DNA-repair machinery
Expression of drug transporter (ABC)
Natural resistance to apoptosis

22. CONTENTS 1- CONCEPT OF CANCER STEM CELLS 2- HISTORY
3- ORIGIN OF CANCER STEM CELLS
4- ISOLATION AND MARKERS
5- ROLE OF CANCER STEM CELLS IN CANCER METASTASIS
6- ROLE OF CANCER STEM CELLS IN DRUG RESISTANCE
7- THERAPUITIC APPLICATIONS

23. RADIOTHERAPY, ROS and CANCER STEM CELLS
Radiotherapy has to potential to damage cell DNA and induce apoptosis through ROS.
Cancer stem cells survive radiotherapy by producing enzymes that protect them against ROS as well as anti apoptotic enzymes

24. resistant to chemotherapeutic agents.
Their niche protects them from coming into contact with large concentrations of anti-cancer drugs.
They express various transmembrane proteins, such as MDR1, that pump drugs out of the cytoplasm.
They divide slowly, like adult stem cells tend to do, and are thus not killed by chemotherapeutic agents that target rapidly replicating cells via damaging DNA or inhibiting mitosis.
They upregulate DNA damage repair proteins.
They are characterized by an overactivation of antiapoptotic signaling pathways.

25. Multidrug Chemoresistance
A series of transporter proteins in the membrane protect against chemotherapy
ABCG2 and BCRP1 were shown to decrease the intra- cellular accumulation of certain chemotherapeutic agents

26. CONTENTS
1- CONCEPT OF CANCER STEM CELLS 2- HISTORY 3- ORIGIN OF CANCER STEM CELLS 4- ISOLATION AND MARKERS 5- ROLE OF CANCER STEM CELLS IN CANCER METASTASIS 6- ROLE OF CANCER STEM CELLS IN DRUG RESISTANCE 7- THERAPUITIC APPLICATIONS

29. Treatment Applications
Tyrosine-kinase inhibitors including Gefitinib and Imatinib, deactivate ABCG2 and supply as candidates to overturn cancer stem cell chemoresistance and potentiallytarget cancer stem cell
According to the cancer stem cell hypothesis, manipulation of the apoptotic machinery of cancer stem cells can be a potential cure to cancer
Eradicating cancer stem cells through targeting their enhanced signaling pathways such NOTCH and Wnt.