Most cancers occur more frequently in males compared to females, yet females have better survival after cancer diagnosis as compared to males. The biological underpinnings for these sex differences in cancer incidence and clinical outcomes are not well understood. While it is hypothesized that these sex differences may be hormone- and/or sex chromosome-dependent, these differences may also be influenced by genetics, epigenetics, and other complex biological phenomena. For example, in brain tumors, a rare but devastating cancer, males are more likely to develop malignant brain tumors than females at all ages, including childhood, suggesting that the sex disparity cannot be explained solely by the effects of circulating sex hormones. Despite several genomic analyses that have identified sex-specific molecular alterations in genetics, epigenetics, cellular (namely macrophages and microglia) behavior, and organ physiology, for some cancers patients still receive the same treatment. Sex differences are not accounted for in the majority of experimental models, not considered in the treatment of cancer, nor accommodated in clinical trial design.

This Research Topic's long-term goal is to expand our knowledge of biological mechanisms of sex differences in cancer and provide a pathway towards sex-specific-based stratification and treatment of cancer patients.

Themes in this Research Topic advocate that tailoring treatments to men and women with cancers based on the sex-specific molecular subtypes of their tumors may improve survival for all patients. Our long-term goal is to identify sex-specific mechanisms that drive cancer and can be leveraged for future therapies that move beyond using the same treatments for all cancer patients to tailoring treatments to the unique vulnerabilities of male versus female patients with cancer.

Original Research, Reviews, and Systematic Reviews (in addition to other article types available in participating sections) in this Research Topic might include, but are not limited to, the following topics:
- Sex differences in the incidence, clinical manifestation, and trajectory of cancer.
- Sex differences in the genetics, epigenetics, and cellular behavior underlying mechanistic differences in tumorigenesis, response to therapy, and disease outcomes.
- Sex-specific biological mechanisms in the tumor microenvironment that drive sex-specific behaviors.
- Preclinical studies illuminating biological mechanisms relevant to sex differences in cancer.
- Drugs that affect the above sex disparities and their impact on treatment.

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Frontiers in Genetics

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