CANCER STEM CELLS Robert Farley University of Rhode

CANCER STEM CELLS Robert Farley University of Rhode Island Department of Biomedical Engineering

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 cells retain the same biological properties as the parent cell) self-renewal is especially notable, because its constant changing is highly relevant to malignancy

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

Stem Cells Forming Various Cell Types

Cancer Stem Cells � � Studies have shown that the characteristics of stem-cell systems 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 have been termed "cancer stem cells“ Just as some forms of cancer cells mutate from certain cells it is possible that cancer stem cells arise by mutation from normal stem cells

Problems caused by Cancer Stem Cells � � Cancer stem cells can be the source of all the malignant cells in a primary tumor They can be the drug-resistant cells that are responsible for relapse after a chemotherapyinduced remission They can give rise to distant metastases 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

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 myelogenous leukemia (CML) and acute myelogenous leukemia (AML) Due to the cancer stem cells, regular treatment of these types of cancer are usually ineffective

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

Chronic Myelogenous Leukemia � � There has been research on drugs that specifically control leukemia-cell growth Certain inhibitors have been used to stop the growth of the CML cells � ABL � � � kinase inhibitor imatinib mesylate 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

Cancer Stem Cells In Breast Cancer � � � Studies have shown that patients with advanced stages of metastatic breast cancer demonstrated that cells with a specific cell-surface antigen could successfully establish 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 tumor inside the mouse whereas the majority of the malignant cells failed to form any type of tumor

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

Challenges � � � Determining how relevant stem cells are in the treatment of all cancers How do different chemotherapy agents affect the evolution of cancer stem cells during conventional treatment? Do different cancer stem cells have different weak points? � determining whether the same tumor-specific mechanisms of growth and survival are active across multiple cancer types

Challenges � � � Will the current forms of treatment provide a competitive advantage for cancer stem cells? 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 will be necessary to improve the outcome of treatment for at least some cancers

Standard Therapy vs Stem Cell Therapy

References � � Jordan, PHD, Craig T. , Monica L. Guzman, PHD, and Mark Noble, PHD. "Cancer Stem Cells. " The New England Journal of Medicine 1261 st 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/2010/01/1001311455 07. htm>. Targeting Cancer at Its Root. Stemline. Web. 26 Mar. 2010. <http: //www. stemline. com/images/csc. Large. gif>.