A tale of sex-specificity in DNA damage response pathways: the paradigmatic story of TSPYL2

Miriana Cardano, Giacomo Buscemi, Laura Zannini
J Sex Gender Specif Med 2024, 10(3): online ahead of print

Abstract. Sexual dimorphism in cancer is still a poorly explored field but it is recognized that differences between males and females should depend not only on hormones and sex chromosomes, but also on molecular pathways generally considered to act equally in both sexes, such as the DNA damage response (DDR). Here, we will describe and discuss the sex specific regulation and function of the DDR protein TSPYL2 in cancer cells. We will highlight how these disparities could contribute to the different cancer predisposition and therapy outcome of males and females and the importance of considering sex in both basic research and clinical practice. Keywords. DNA damage response, sex chromosomes, cancer.