Linking DNA Damage and Hormone Signaling Pathways in Cancer

DNA damage response and repair (DDR) is a tightly controlled process that serves as a barrier to tumorigenesis. Consequently, DDR is frequently altered in human malignancy, and can be exploited for therapeutic gain either through molecularly targeted therapies or as a consequence of therapeutic agents that induce genotoxic stress. In select tumor types, steroid hormones and cognate receptors serve as major drivers of tumor development/progression, and as such are frequently targets of therapeutic intervention. Recent evidence suggests that the existence of crosstalk mechanisms linking the DDR machinery and hormone signaling pathways cooperate to influence both cancer progression and therapeutic response. These underlying mechanisms and their implications for cancer management will be discussed.

TrendsControversy exists whether hormones are genotoxic or are protective of damage.Hormone/nuclear receptor signaling positively regulates DNA double-strand break repair in cancer.Several components of the DNA damage response and repair machinery influence nuclear receptor transcriptional function in models of malignancy.DNA repair–hormone signaling crosstalk represents an underappreciated and potentially vast opportunity for further studies in cancer biology: basic, translational, and clinical.