Sex differences in cancer

Sex differences impact various non-reproductive organ cancers, often leading to higher cancer incidence and poorer outcomes in male individuals. In this Perspective article, Xiao, Lee et al. outline the biological factors contributing to sex bias in immuno-oncology, emphasizing the need for future research to offer a fuller understanding of sex disparities in cancer.

Sex steroids are major promoters of the growth of breast and prostate cancers. This Review by Poutanen et al. describes the development of treatments for these cancer types that act to restrict sex steroid availability for receptor binding by inhibiting steroid biosynthesis, being a complementary mechanism of action to the more traditional sex steroid antagonists.

The concurrence of cancer and pregnancy can pose complex medical, psychosocial and ethical issues. In this Comment, Varella and Partridge present approaches to the treatment of cancer during pregnancy, with a focus on patient preferences, patient and fetal risks, and team-based management.

In this Comment, Berna Özdemir summarizes the evidence for greater drug toxicity in female patients and emphasizes the need for increased awareness of sex differences at all stages of drug development to establish sex-specific anticancer treatment strategies.

Pregnancy-associated breast cancers are typically diagnosed at more advanced stages than other breast cancers. Recently, Saura et al. developed a non-invasive screening method using breast milk to diagnose patients prior to tumour detection by imaging.

Two independent studies published in Nature have collectively addressed the long-standing question of sex bias in cancer and implicated non-hormonal genes of the Y chromosome in aggressive features of colorectal and bladder cancers in men.

In a comprehensive study in acute myeloid leukaemia, Ozga et al. demonstrate sex-specific differences in the frequency and prognostic effect of genetic alterations.

This Perspective highlights the evidence from basic and translational research that genetic sex influences multiple factors that can contribute to cancer development and treatment responses, and suggests that including genetic sex considerations in treatments for patients with cancer will improve outcomes.

Two studies have now provided evidence of differences, dependent on patient sex, in oncogenic features, such as frequencies of driver gene mutations, mutation load and mutational signatures, as well as immune selection.

The incidence of early-onset colorectal cancer (EOCRC) continues to rise and disproportionately affects people of African descent. This Comment advocates for mechanistic studies that can help mitigate EOCRC disparities.

The incidence of many cancer types in non-reproductive tissues is higher in males than in females. This Opinion article discusses the cellular and molecular differences between the two sexes that might contribute to this discrepancy.