Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

3.2 Brain Cancer Stem Cells Introduction
CDK1 and CDK2 was significantly higher in CD133 + cells than in CD133 - cells,
indicating that the former show greater checkpoint activation in response to
DNA damage. The fact that CD133 + glioma cells demonstrated to activate
checkpoint responses to a greater extent than CD133 - cells, suggested that the
resistance of CD133 + cells to ionizing radiation is due to preferential check-
point activation. The finding that CD133 + cells were made less resistant to
radiation if the checkpoint kinases CDK1 and CDK2, which control the pauses
in cell-cycle progression that are scheduled for DNA repair to occur (Fig 3.3),
were to be pharmacologically inhibited, provided the potential for a cure tar-
geting the resilient stem cell mass. The CD133 + resistant population should be
Figure 3.3: The cell cycle of eukaryotic cells can be divided into four successive
phases: M for mitosis, S for DNA synthesis, and two gap phases, G1 and G2. In
the G1 phase extracellular cues may induce either commitment to a further round of
cell division or withdrawal from the cell cycle into G0 to embark on a differentiation
pathway. The G1 phase is also involved in the control of DNA integrity before the
onset of DNA replication. During the G2 phase the cell checks the completion of
DNA replication and the genomic integrity before cell division starts. Adapted from
Dehay et al 2007 [115].
targeted with DNA checkpoint blockers to make these cells radiosensitive and
thus, in one therapy cycle, potentially wipe out the entire tumour mass (Fig
3.4) [123]. Together, the results exposed by Bao et al showed that CD133 +
cancer cells contributed to glioma radioresistance and tumour re-population
through preferential checkpoint response and DNA repair, and targeting of
checkpoint response in CD133 + cancer cells can overcome glioma radioresis-
tance in vitro and in vivo, which may provide a therapeutic advantage to
reduce brain tumour recurrence [40].
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