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The glioblastoma cells with stem-like features survive radiotherapy better than the rest of the tumour because they repair DNA damage more efficiently, which helps explain why the cancer returns after treatment and points to checkpoint inhibitors as a way to sensitise it.
Bao, Rich and colleagues showed that CD133-positive glioma cells, the fraction with stem cell properties, became enriched after ionising radiation both in mouse xenografts and in patient specimens. These cells activated the DNA damage checkpoint proteins ATM, Rad17, Chk1 and Chk2 more strongly and repaired radiation-induced DNA damage more effectively than CD133-negative cells. Blocking Chk1 and Chk2 with a small molecule reversed the radioresistance, suggesting a way to target the cells that survive standard treatment.
This paper connected the cancer stem cell idea to a clinical problem, the near-universal recurrence of glioblastoma after radiotherapy, and gave a mechanism and a drug target. It is part of the rationale for combining radiotherapy with DNA damage response inhibitors now in trials.
Shares Reya 2001: stem cells, cancer and cancer stem cells, Stem cell, Recurrence and relapse.
Shares Stem cell, Radiotherapy.
Shares Singh 2004: identification of human brain tumour initiating cells, Reya 2001: stem cells, cancer and cancer stem cells, Glioma & glioblastoma.
Shares Singh 2004: identification of human brain tumour initiating cells, Glioma & glioblastoma.
Shares Singh 2004: identification of human brain tumour initiating cells, Stem cell.
Shares Stem cell, Recurrence and relapse.