Combined androgen deprivation with radiotherapy for prostate cancer: does it make sense?

Abstract

Currently, our understanding of the mechanism(s) of radiation-induced death of prostate cancer is limited. In-depth analysis of these processes would facilitate the design of more effective treatment strategies utilizing radiation therapy. An increasingly recognized form of radiation-induced death is postmitotic apoptosis. In this process, radiation damages the tumor cell s DNA. The cell then divides prior to completing DNA repair, an event that is lethal. In order to avoid this fate, the cancer cell may attempt to halt its cell-cycle machinery temporarily to repair its DNA prior to dividing. In the treatment of prostate cancer, radiation therapy currently is being evaluated in combination with androgen deprivation (AD). However, because AD can induce growth arrest, it may reduce the effectiveness of radiation through a reduction in postmitotic apoptosis. To study this effect, we examined the effect of AD on prostate cancer radiosensitivity as it is related to cell-cycle progression. Androgen-sensitive prostate cancer cells demonstrated increased resistance to radiation when deprived of androgenic stimuli. Thus, paradoxically, AD may reduce the radiosensitivity of prostate cancer by means of cell-cycle delay, which results in a reduction in postmitotic apoptosis.