TY - JOUR
T1 - The PI-3kinase pathway in hematopoietic stem cells and leukemia-initiating cells
T2 - A mechanistic difference between normal and cancer stem cells
AU - Yilmaz, Ömer H.
AU - Morrison, Sean J.
N1 - Funding Information:
This work was supported by the Howard Hughes Medical Institute. O.H.Y. was supported by a Medical Scientist Training Program Fellowship.
PY - 2008/7
Y1 - 2008/7
N2 - The identification of cancer stem cells in leukemia, breast, brain, colon, and other cancers suggests that many tumors are maintained by stem cells in much the same way as normal tissues are maintained. Because cancer stem cells share remarkable phenotypic and functional similarities with normal stem cells, it may be difficult to identify therapeutic approaches to kill cancer stem cells without killing the normal stem cells in the same tissue. Yet in certain tissues, like the hematopoietic system and gut epithelium, this will be critical as regenerative capacity in these tissues is acutely required for life. Components of the PI-3kinase pathway, including Akt, mTor and FoxO are critical regulators of both normal stem cell function and tumorigenesis. Intriguingly, inactivation of some pathway components, like Pten, has opposite effects on normal hematopoietic stem cells (HSCs) and leukemia-initiating cells. This raises the possibility that drugs targeting this pathway could be more effective at eliminating cancer stem cells while being less toxic against normal stem cells.
AB - The identification of cancer stem cells in leukemia, breast, brain, colon, and other cancers suggests that many tumors are maintained by stem cells in much the same way as normal tissues are maintained. Because cancer stem cells share remarkable phenotypic and functional similarities with normal stem cells, it may be difficult to identify therapeutic approaches to kill cancer stem cells without killing the normal stem cells in the same tissue. Yet in certain tissues, like the hematopoietic system and gut epithelium, this will be critical as regenerative capacity in these tissues is acutely required for life. Components of the PI-3kinase pathway, including Akt, mTor and FoxO are critical regulators of both normal stem cell function and tumorigenesis. Intriguingly, inactivation of some pathway components, like Pten, has opposite effects on normal hematopoietic stem cells (HSCs) and leukemia-initiating cells. This raises the possibility that drugs targeting this pathway could be more effective at eliminating cancer stem cells while being less toxic against normal stem cells.
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U2 - 10.1016/j.bcmd.2008.02.004
DO - 10.1016/j.bcmd.2008.02.004
M3 - Article
C2 - 18387833
AN - SCOPUS:44649190505
SN - 1079-9796
VL - 41
SP - 73
EP - 76
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
IS - 1
ER -