Linking DNA Damage and Hormone Signaling Pathways in Cancer

Abstract

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.

Keywords: DNA repair; cancer; hormones; nuclear receptor; transcription.

Figure 1

Nuclear Receptors (NRs) regulate key DNA repair factors, and DNA repair factors influence NR function. Top (above the hashed line): DNA repair factors shaded in blue are those which are positively regulated by the indicated NR as depicted by the arrow and + sign, or negatively regulated by the indicated NR as depicted by the block line. Bottom (below the hashed line): Indicated DNA repair factors known to harbor effects on NRs are indicated. Text depicts how these DNA repair factors regulate NR function, and the biological outcomes are indicated in italics. Abbreviations: ERα, estrogen receptor α; ERβ, estrogen receptor β; AR, androgen receptor; PR, progesterone receptor; PCa, prostate cancer; BrCa, breast cancer.