Abstract:
:Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequently occurs in PFA ependymomas, suppresses homologous recombination (HR)-mediated DNA repair. Mechanistically, CXorf67 interacts with PALB2 and inhibits PALB2-BRCA2 interaction, thereby inhibiting HR repair. Concordantly, tumor cells with high CXorf67 expression levels show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with radiotherapy. Thus, our findings have revealed a role of CXorf67 in HR repair and suggest that combination of PARP inhibitors with radiotherapy could be an effective treatment option for PFA ependymomas.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Han J,Yu M,Bai Y,Yu J,Jin F,Li C,Zeng R,Peng J,Li A,Song X,Li H,Wu D,Li Ldoi
10.1016/j.ccell.2020.10.009subject
Has Abstractpub_date
2020-12-14 00:00:00pages
844-856.e7issue
6eissn
1535-6108issn
1878-3686pii
S1535-6108(20)30540-7journal_volume
38pub_type
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