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NF1 Reveals New Methods for Malignant Brain Tumor Treatment Resistance


A representative specimen from one adult with a glioblastoma reveals increased ABCG1 expression relative to one representative agematched control brain. Scale bar, 50 μm.

The overall survival for adults with malignant glioma (glioblastoma) remains poor despite numerous exciting advances in radiation and chemotherapy. One of the ways that brain cancer cells become resistant to treatment involves increasing their ability to withstand stress. Previous studies by Dr. Yi-Hsien Chen have revealed that a protein called ABCG1 is critical for mediating mouse Nf1 optic glioma stem cell survival. In these low-grade brain tumors, ABCG1 works to suppress brain optic glioma cell stress responses.
Since some malignant brain tumors (glioblastoma) arising in people without NF1 harbor mutations in the NF1 gene, Dr. Chen sought to determine whether ABCG1 could be important for glioblastoma survival. In this new report, he showed that ABCG1 expression is increased in human adult glioblastoma, where it correlates with poor patient survival. Next, using a mouse model of glioblastoma, he demonstrated that silencing of Abcg1 expression resulted in greater glioma cell death. Finally, he showed that reducing Abcg1 levels attenuated glioblastoma growth and increased mouse survival.
Together, these exciting results establish that ABCG1 is essential for malignant glioma survival, and might serve as a future therapeutic target for these deadly brain cancers.
Chen YH, Cimino PJ, Luo J, Dahiya S, Gutmann DH. ABCG1 maintains high-grade glioma survival in vitro and in vivo. Oncotarget. 2016 Mar 10. doi: 10.18632/oncotarget.8030. [Epub ahead of print]