{"entity":{"id":"paper-bao-glioma-stem-cells-radioresistance-nature-2006","kind":"paper","name":"Bao 2006: glioma stem cells resist radiotherapy by activating the DNA damage response","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1038/nature05236"}],"tags":[],"related":["paper-reya-cancer-stem-cells-nature-2001"],"cancers":["glioblastoma"],"sections":[],"technologies":[],"targets":["atr"],"drugs":[],"companies":[],"institutions":["duke-cancer-institute"],"pathways":[],"terms":["stem-cell","radiotherapy","relapse-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Nature","year":2006,"doi":"10.1038/nature05236","authors":"Bao S, Wu Q, McLendon RE, et al.","paperType":"basic","findings":["CD133-positive glioma cells were enriched after radiation in xenografts and in patient tumours.","These cells showed preferential activation of the DNA damage checkpoint (ATM, Rad17, Chk1, Chk2) and more effective DNA repair.","A Chk1 and Chk2 inhibitor reversed the radioresistance of the CD133-positive cells."],"whatItMeans":"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.","caveats":["CD133 is an imperfect marker of glioma stem cells and CD133-negative cells can also initiate tumours.","Mouse xenograft and cell line work; the clinical benefit of checkpoint inhibition with radiotherapy is not yet proven."],"changedPractice":false},"route":"/key-papers/paper-bao-glioma-stem-cells-radioresistance-nature-2006/","neighbours":{"paper":[{"id":"paper-reya-cancer-stem-cells-nature-2001","kind":"paper","name":"Reya 2001: stem cells, cancer and cancer stem cells","route":"/key-papers/paper-reya-cancer-stem-cells-nature-2001/"},{"id":"paper-singh-brain-tumour-initiating-cells-nature-2004","kind":"paper","name":"Singh 2004: identification of human brain tumour initiating cells","route":"/key-papers/paper-singh-brain-tumour-initiating-cells-nature-2004/"}],"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"target":[{"id":"atr","kind":"target","name":"ATR","route":"/targets/atr/"}],"institution":[{"id":"duke-cancer-institute","kind":"institution","name":"Duke Cancer Institute","route":"/institutions/duke-cancer-institute/"}],"term":[{"id":"radiotherapy","kind":"term","name":"Radiotherapy","route":"/terms/radiotherapy/"},{"id":"relapse-recurrence","kind":"term","name":"Recurrence and relapse","route":"/terms/relapse-recurrence/"},{"id":"stem-cell","kind":"term","name":"Stem cell","route":"/terms/stem-cell/"}]}}