The emerging regulatory interface between DNA repair and steroid hormone receptors in cancer.

Human cells potentiate highly diverse functions through tight transcriptional regulation and maintenance of genome integrity. While the DNA damage response (DDR) safeguards the genome, ligand-activated transcription factors, such as steroid hormone receptors (SHRs), provide complex transcriptional outputs. Interestingly, an increasing body of evidence reveals a direct biological and functional interplay between DDR factors and SHR cascades in cancer. SHRs can directly affect DDR gene expression, but DDR factors in turn act as transcriptional coregulators, enabling oncogenic SHR-mediated signaling, which has the potential for novel therapeutic interventions. With a focus on breast and prostate cancer, we describe in this review recent developments in, and insights into, the complex interplay between SHR signaling and the DDR, highlighting opportunities for future clinical interventions.