Double edged sword of TOP2B mediated double strand breaks: both oncogenic force and Achilles heel

Prostate cancer cells are dependent on Androgen Receptor (AR) mediated transcriptional programs for their growth and survival. We have shown that efficient induction of the full AR transcriptional programs by hormone stimulation requires the action of TOP2B, which is likely involved in resolving topological constraints arising at each step of transcriptional initiation, elongation and termination of the induced programs. Interestingly, these processes also lead to formation of TOP2B-mediated double strand breaks, which can seed formation of genomic rearrangements. Opportunistically, we can also exploit these double strand breaks as an Achilles heel to develop therapeutic strategies for prostate and potentially other cancers.