Fig. 1

Sex-specific epigenetic programming may contribute to differential barriers to tumorigenesis in males and females. Divergence in male and female epigenetics begins from the moment of fertilization, driven by differences in sex chromosome gene expression and metabolic profiles between XX and XY embryos. Throughout development, additional processes, such as X-chromosome inactivation and gonadal steroid exposure, further differentiate the sexes. The unique epigenetic landscapes of male and female cells may contribute to sex differences in the barrier to tumorigenesis, as well as to sex differences in tumor heterogeneity and response to treatments—both conventional and epigenetic targeted