Sex steroid hormones and DNA repair regulation: Implications on cancer treatment responses

Abstract

The role of sex steroid hormones (SSHs) has been shown to modulate cancer cytotoxic treatment sensitivity. Dysregulation of DNA repair associated with genomic instability, abnormal cell survival and not only promotes cancer progression but also resistance to cancer treatment. The three major SSHs, androgen, estrogen, and progesterone, have been shown to interact with several essential DNA repair components. The presence of androgens directly regulates key molecules in DNA double-strand break (DSB) repair. Estrogen can promote cell proliferation and DNA repair, allowing cancer cells to tolerate chemotherapy and radiotherapy. Information on the role of progesterone in DNA repair is limited: progesterone interaction with some DNA repair components has been identified, but the biological significance is still unknown. Here, we review the roles of how each SSH affects DNA repair regulation and modulates response to genotoxic therapies and discuss future research that can be beneficial when combining SSHs with cancer therapy. We also provide preliminary analysis from publicly available databases defining the link between progesterone/PR and DDRs & DNA repair regulation that plausibly contribute to chemotherapy response and breast cancer patient survival.

Keywords: Androgen; Chemotherapy; DNA damage responses; DNA repair; Estrogen; Progesterone.