Biomedical Engineering Reference
In-Depth Information
Lessons Learned from Leukemia
From leukemia we have learned that the genetic lesions of cancer occur in the
stem cells, and that the expression of these lesions later in the lineage of the
white blood cells determines the stage of differentiation of the leukemia.
Chemo- and radiotherapies act on the leukemic transit-amplifying cells, but
the cancer stem cells are resistant. Newly developed techniques of targeted
interference with the proliferation signals, or use of apoptosis inhibitors
responsible for the maturation arrest, can allow terminal differentiation of
leukemic cells.
3 Cancer Stem Cell-Directed Therapy
Regardless of whether cancers are maintained by stem cells or by a population
of cells that are in G 0 at the time of treatment, the properties of the treatment-
resistant cells can be exploited, in efforts to eliminate the therapy-resistant
cells. The rationale for this approach is presented in Fig. 3 (Sell, 2006a,c,
2007a).
1. RADIATION THERAPY
2. CHEMOTHERAPY
3. ANTI-ANGIOGENIC THERAPY
LEVELS OF THERAPY
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4. DIFFERENTIATION THERAPY
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5. STEM CELL INHIBITION
Fig. 3 Differentiation therapy of cancer stem cells. Chemotherapy, radiotherapy, and anti-
angiogenic therapy are directed at the actively proliferating transit-amplifying cells of a
cancer. When these therapies are discontinued, the cancer regrows from the therapy-resistant
cancer stem cells. Differentiation therapy blocks the activation signals, causing maturation
arrest. However, when differentiation therapy is discontinued, the cancer will re-form from
the cancer progenitor cells. Stem cell inhibition is directed against the signals that keep a
cancer stem cell a stem cell. By blocking or reversing the stemness signals, it may be possible to
force the cancer stem cell to differentiate. From Sell (2006a)
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