Editors' ChoiceCancer

To beam or not to beam

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Science Translational Medicine  21 Oct 2015:
Vol. 7, Issue 310, pp. 310ec179
DOI: 10.1126/scitranslmed.aad4448

When prostate cancer is deprived of androgen stimulation, it becomes more sensitive to radiation therapy, in part through inhibition of the DNA repair machinery. This explains why prostate cancer patients do better when androgen deprivation therapy is added to their external beam radiation treatment. But recent reports suggest that, in a subset of prostate cancer patients, radiation therapy can actually up-regulate androgen receptor signaling, a potentially undesirable effect. A new report by Spratt et al. examines what this observation means for the use of androgen deprivation therapy after radiation treatment.

In this study, the authors studied the effect of radiation therapy on androgen receptor signaling in multiple human prostate cancer models in vitro and in vivo. The authors showed that radiation therapy up-regulated androgen receptor expression and activity in four human prostate cancer cell lines and that the magnitude of the up-regulation correlated with increased tumor viability. These findings were confirmed in xenograft tumors; androgen receptor mRNA and protein increased within 24 hours of radiation and were generally elevated for at least 9 days. Moreover, the tumors with the greatest percent increase in androgen receptor signaling grew more rapidly. Similarly, in 227 patients with prostate cancer, 40 (18%) showed an increase in androgen receptor–regulated targets such as serum-free-HK2 (human glandular kallikrein 2) after radiation. These patients were more likely to experience an increase in PSA (a marker of prostate cancer) than the patients with unchanged or declining HK2.

These results address concerns about the indiscriminate use of androgen deprivation therapy. Measurements of androgen receptor activity during and after combined androgen-deprivation and radiation therapy could identify those men with increased radiation-induced androgen signaling, enabling selection of the patients most likely to benefit from further androgen-deprivation therapy.

D. E. Spratt et al., Androgen receptor upregulation mediates radioresistance after ionizing radiation. Cancer Res. 10.1158/0008-5472.CAN-15-0892 (2015). [Abstract]

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