TAILIEUCHUNG - Chapter 080. Cancer Cell Biology and Angiogenesis (Part 13)

New Concepts in the Development of Cancer Therapeutics Cancer Stem Cells It has long been recognized that only a small proportion of the cells within a tumor are capable of initiating colonies in vitro or of forming tumors at high efficiency when injected into immunocompromised NOD/SCID mice. Current work indicates that human acute and chronic myeloid leukemias (AML and CML) have a small population of cells ( | Chapter 080. Cancer Cell Biology and Angiogenesis Part 13 New Concepts in the Development of Cancer Therapeutics Cancer Stem Cells It has long been recognized that only a small proportion of the cells within a tumor are capable of initiating colonies in vitro or of forming tumors at high efficiency when injected into immunocompromised NOD SCID mice. Current work indicates that human acute and chronic myeloid leukemias AML and CML have a small population of cells 1 that have properties of stem cells such as unlimited self-renewal and the capacity to cause leukemia when serially transplanted in mice. These cells have an undifferentiated phenotype Thyl-CD34 CD38- and negative for other differentiation markers and resemble normal stem cells in many ways but are no longer under homeostatic control Fig. 80-7 . Solid tumors may also contain a population of stem cells. Cancer stem cells like their normal counterparts have unlimited proliferative capacity and paradoxically traverse the cell cycle at a very slow rate cancer growth occurs largely due to expansion of the stem cell pool the unregulated proliferation of the transit amplifying population and failure of apoptosis pathways Fig. 80-7 . Slow cell cycle progression plus high levels of expression of anti-apoptotic Bcl-2 family members and drug efflux pumps of the MDR family render cancer stem cells less vulnerable to cancer chemotherapy or radiation therapy. Implicit in the cancer stem cell hypothesis is the idea that failure to cure most human cancers is due to the fact that current therapeutic agents do not kill the stem cells. If cancer stem cells can be identified and isolated then aberrant signaling pathways that distinguish these cells from normal tissue stem cells can be identified and targeted. Oncologists eagerly await a new class of agent that may directly attack the cells that drive tumor growth. Figure 80-7 Cancer stem cells play a critical role in the initiation progression and resistance to therapy of .

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