Cancer Stem Cells

1. Cancer Stem Cells Robert Farley University of Rhode Island Department of Biomedical Engineering

2. Stem Cells • Stem cells have unique features • Un-specialized • Ability to form any cell • Can divide themselves for long periods of time • Self-renewal (at cell division, one or both daughter cellsretain the same biological properties as the parent cell) • self-renewal is especiallynotable, because its constant changing is highly relevant to malignancy

3. Cancer Cells • Mutation of normal cells • “Normal” cells will group together to form different types of tissue • Like normal cells, cancer cells will also group together forming tumors • Tumors can either be malignant or benign • Malignant – cancerous

4. Stem Cells Forming Various Cell Types

5. Cancer Stem Cells • Studies have shown that the characteristics of stem-cellsystems and/or the specific stem-cell properties are relevant to some forms of human cancer • These properties of “tumor-initiating” cells have similar properties to stem cells • Cancerous cells with these functional properties havebeen termed "cancer stem cells“ • Just as some forms of cancer cells mutate from certain cells it is possible that cancer stem cellsarise by mutation from normal stem cells

6. Problems caused by Cancer Stem Cells • Cancer stem cells can be the source of all the malignant cellsin a primary tumor • They can be thedrug-resistant cells that are responsible for relapse aftera chemotherapy-induced remission • They can give rise to distantmetastases • Because stem cells have the characteristic to form any type of cell, cancer stem cells have the ability to perform any of the actions mentioned above

7. Cancer Stem Cells in the Hematopoietic System • Hematopoietic System contains organs and tissue with the main focus being the lymph nodes, spleen and bone marrow • One of the most prevalent types of cancer involved in this system is Leukemia • Cancer stem cells are evident in chronic myelogenousleukemia (CML)and acute myelogenous leukemia (AML) • Due to the cancer stem cells, regular treatment of these types of cancer are usually ineffective

8. Acute Myelogenous Leukemia • AML cancer stem cells have surface markers,such as the interleukin-3–receptor • This specific receptor is not found on the normal stem cell • This marker is useful for antibody based therapeutic treatment • Scientists hope that by using this receptor to target the cancer stem cells, treatment for AML will be more effective

9. Chronic MyelogenousLeukemia • There has been research on drugs that specificallycontrol leukemia-cell growth • Certain inhibitors have been used to stop the growth of the CML cells • ABL kinase inhibitor imatinibmesylate • However, drugs do not kill the CML cells therefore allowing the cancer to relapse after therapy is finished • The cancer stem cells are responsible for the replapse • By targeting the cancer stem cells involved with CML treatment should become more effective

10. Cancer Stem Cells In Breast Cancer • Studies have shown that patients with advanced stages of metastaticbreast cancer demonstrated that cells with a specific cell-surfaceantigen could successfullyestablish themselves as tumor xenografts • Experiment done with immunodeficient mice where human breast cancer cells were implanted into the mammary fat pad of the mouse • Experiment showed that only the cancer stem cells could successfully grow the tumorinside the mouse whereas the majority of the malignant cells failed to form any type of tumor

11. Future for Breast Cancer • By showing that the cancer stem cells can act as xenografts, it gives scientists another way to differentiate between normal stem cells and cancer stem cells • By categorizing these stem cells due to the properties they possess it is easier to explain how cancer stem cells work • Like cancer stem cells in leukemia, much work is to be done with breast cancer as well

12. Challenges • Determining how relevant stem cells are in the treatment of all cancers • How do different chemotherapyagents affect the evolution of cancer stem cells during conventionaltreatment? • Do different cancer stem cells have different weak points? • determining whether the same tumor-specific mechanismsof growth and survival are active across multiple cancer types

13. Challenges • Will the current forms of treatment provide a competitive advantage for cancer stemcells? • Will targeting self renewal cells kill them or just suppress them during treatment? • However, doctors and scientists feel strongly that the eradication of cancer stem cells willbe necessary to improve the outcome of treatment for at leastsome cancers

14. Standard Therapy vs Stem Cell Therapy

15. References • Jordan, PHD, Craig T., Monica L. Guzman, PHD, and Mark Noble, PHD. "Cancer Stem Cells." The New England Journal of Medicine 1261st ser. 355.1253 (2006) • Wikipedia. Stem Cells. Web. 25 Mar. 2010. <http://en.wikipedia.org/wiki/Stem_cell>. • Targeting Cancer Stem Cells in the Lab. Science Daily. Web. 25 Mar. 2010.<http://www.sciencedaily.com/releases/2010/01/100131145507.htm>. • Targeting Cancer at Its Root. Stemline. Web. 26 Mar. 2010. <http://www.stemline.com/images/cscLarge.gif>.