AI Article Synopsis
- Diffuse intrinsic pontine glioma (DIPG) is the most lethal brain tumor in children, with current treatments focusing on palliative radiotherapy despite various drug trials.
- Using Cre/loxP technology, researchers demonstrated that deleting the Ataxia telangiectasia mutated (Atm) gene in mouse models can make tumors more sensitive to radiation therapy, particularly in p53-deficient gliomas.
- The study indicates that the tumor's genetic makeup influences the effectiveness of combining ATM inhibition with radiation, suggesting tailored treatment strategies for different DIPG genotypes.
Article Abstract
Diffuse intrinsic pontine glioma (DIPG) kills more children than any other type of brain tumor. Despite clinical trials testing many chemotherapeutic agents, palliative radiotherapy remains the standard treatment. Here, we utilized Cre/loxP technology to show that deleting Ataxia telangiectasia mutated (Atm) in primary mouse models of DIPG can enhance tumor radiosensitivity. Genetic deletion of Atm improved survival of mice with p53-deficient but not p53 wild-type gliomas after radiotherapy. Similar to patients with DIPG, mice with p53 wild-type tumors had improved survival after radiotherapy independent of Atm deletion. Primary p53 wild-type tumor cell lines induced proapoptotic genes after radiation and repressed the NRF2 target, NAD(P)H quinone dehydrogenase 1 (Nqo1). Tumors lacking p53 and Ink4a/Arf expressed the highest level of Nqo1 and were most resistant to radiation, but deletion of Atm enhanced the radiation response. These results suggest that tumor genotype may determine whether inhibition of ATM during radiotherapy will be an effective clinical approach to treat DIPGs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773366 | PMC |
| http://dx.doi.org/10.1172/JCI142158 | DOI Listing |
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