Radiotherapy is more effective in patients with prostate cancer who receive neoadjuvant chemical castration, but the underlying molecular mechanism has been unclear. A study by Helleday and colleagues reveals that castration enhances the radiosensitivity of prostate cancer cells by reducing non-homologous end joining (NHEJ) repair of DNA double-strand breaks (DSBs). In samples from patients receiving castration treatment prior to radiotherapy, levels of the NHEJ protein KU70 and activity of DNA-PK — a kinase required for NHEJ — were significantly reduced, and there were significantly increased levels of the DSB markers γH2AX and 53BP1. The authors thus implicate defective NHEJ repair in castration-induced radiosensitization.
References
Tarish, F. L. et al. Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair. Sci. Transl Med. 7, 312re11 (2015)
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Shipman, L. Radiosensitization through reduced DNA repair. Nat Rev Cancer 15, 697 (2015). https://doi.org/10.1038/nrc4051
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DOI: https://doi.org/10.1038/nrc4051