Why sex and gender matter in cancer research and care.

BACKGROUND: Biological sex and gender significantly influence cancer incidence, biology, disease progression, treatment response, and long-term survival. These differences arise from a complex interplay of hormonal, genetic, epigenetic, immunological, and behavioral factors. Notable disparities have been observed in colorectal, lung, and bladder cancers - including histological subtypes, immune responses, and treatment outcomes. Women are more susceptible to chemotherapy toxicity, often face delayed diagnosis, and experience higher psychosocial burden. In contrast, men tend to show higher cancer-related morbidity and mortality. Transgender and non-binary individuals remain largely underrepresented in cancer research. Furthermore, preclinical models frequently overlook the sex of animal or cellular samples, limiting translational relevance. Emerging technologies - such as multi-omics approaches, 3D human organoids, and artificial intelligence - provide promising tools to better understand sex-specific mechanisms in cancer development and treatment, and will enable future personalization of oncological care according to the patient's sex.

PURPOSE: This review aims to summarize current knowledge on the influence of biological sex and gender on cancer incidence, tumor biology, and therapeutic response, with additional focus on behavioral and psychosocial factors. Special attention is given to colorectal, lung, and bladder cancers as model malignancies with sex-specific differences, and to the ongoing challenges in preclinical research and clinical practice.

CONCLUSION: Sex and gender are key determinants of oncological outcomes and should be systematically incorporated into research design, clinical trial methodology, personalized therapy, and health policy. Their integration is not only a scientific imperative but also an ethical necessity on the path toward precise and equitable cancer care.