Gender Oncology: Rethinking Cancer Through a Sex- and Gender-Based Lens

Background: Gender medicine is an emerging approach that recognizes how biological sex, gender identity, and sociocultural roles influence health and disease. These factors can significantly affect prevention, screening, diagnosis, and treatment outcomes. In oncology, accumulating evidence highlights sex-based differences in cancer incidence, therapeutic response, and treatment-related adverse events. A comprehensive gender-based approach should also address the specific needs of sexual and gender minority (SGM) populations. Based on the existing literature and the authors' expertise, this perspective paper provides an overview of this topic, emphasizing its importance, discussing current challenges, and proposing potential future directions for research and clinical practice. The literature discussed in this article was selected through a narrative, rather than a systematic, approach and is intended to provide the scientific context supporting the authors' perspective and interpretation of the current evidence. Methods: To investigate gender differences in oncology regarding epidemiological data, we queried the AIRTUM and GLOBOCAN databases. Furthermore, we conducted a bibliography search of scientific papers by querying PubMed/MEDLINE to explore gender differences, in particular regarding treatments. The database was searched by looking for papers published between 1 January 2022 and 31 December 2025. Results: Cancers affecting both sexes show higher incidence and mortality rates in men, a trend observed worldwide and confirmed by national data. However, important sex-related differences also emerge in treatment response. Women appear to derive a smaller survival benefit than men from immunotherapy alone but may experience greater benefit when immunotherapy is combined with chemotherapy. These differences may be explained by distinct molecular mechanisms underlying antitumor immune responses in males and females. Furthermore, women experience higher rates of treatment-related toxicities, likely due to sex-specific differences in pharmacokinetics and pharmacodynamics. Conclusions: Integrating sex and gender perspectives into oncology is essential for advancing personalized medicine and improving patient care. Understanding biological differences can help optimize treatment selection and dosing strategies, thereby enhancing efficacy while minimizing adverse effects. At the same time, addressing gender-related factors may improve psychosocial support, patient well-being, and treatment adherence. Achieving these goals requires coordinated efforts, including sex-disaggregated research, gender-sensitive clinical protocols, and healthcare policies aimed at reducing gender disparities in cancer care.