Editors' ChoiceCancer

Giving radiotherapy a boost

Sci. Signal.  10 Nov 2015:
Vol. 8, Issue 402, pp. ec337
DOI: 10.1126/scisignal.aad8180

Androgen deprivation therapy (castration) combined with radiotherapy improves the overall response to radiotherapy in patients with localized intermediate- and high-risk prostate cancer. Tarish et al. biopsied prostate cancer patients at diagnosis and before and after castration and radiotherapy treatments to monitor the molecular events that might explain this improved response. Castration impaired DNA double-strand break repair specifically in prostate cancer tissue by reducing the abundance of the protein Ku70, which is necessary for DNA repair through nonhomologous end joining. This correlated with an increase in unrepaired DNA double-strand breaks caused by radiotherapy, explaining how castration improved the response to radiotherapy. These findings provide mechanistic insight into why castration improves the overall response to radiotherapy in prostate cancer patients.

F. L. Tarish, N. Schultz, A. Tanoglidi, H. Hamberg, H. Letocha, K. Karaszi, F. C. Hamdy, T. Granfors, T. Helleday, Castration radiosensitizes prostate cancer tissue by impairing DNA double-strand break repair. Sci. Transl. Med. 7, 312re11 (2015). [Abstract]