Robert Farley University of Rhode Island Department of Biomedical Engineering

 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

 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

 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

 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 chemotherapy- induced 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

 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

 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

 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

 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

 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

 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

 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

 Jordan, PHD, Craig T., Monica L. Guzman, PHD, and Mark Noble, PHD. "Cancer Stem Cells." The New England Journal of Medicine 1261st ser (2006)  Wikipedia. Stem Cells. Web. 25 Mar  Targeting Cancer Stem Cells in the Lab. Science Daily. Web. 25 Mar  Targeting Cancer at Its Root. Stemline. Web. 26 Mar