Journal
NATURE REVIEWS CANCER
Volume 21, Issue 6, Pages 393-407Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41568-021-00348-y
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Funding
- Sister Institution Network Fund (SINF)
- MD Anderson-Peter MacCallum Cancer Centre
- Peter MacCallum Foundation
- National Institutes of Health (NIH) Specialized Center of Research Excellence [U54AG062333]
- NIH Center of Excellence in Influenza Research and Surveillance [HHSN272201400007C]
- NIH [R01 CA174737]
- Barnard Research Funds
- Children's Discovery Institute of Washington University
- Prayers for Maria Foundation
- St Louis Children's Hospital Foundation
- Barnes-Jewish Hospital Foundation
- Joshua's Great Things Foundation
- American Brain Tumor Association
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Genetic sex plays a significant role in cancer development and treatment responses, and including genetic sex considerations in cancer treatments can lead to improved outcomes. It is important to consider sex chromosomes and gender differences in cancer risk when providing standard care for patients.
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. Curing cancer through precision medicine is the paramount aim of the new wave of molecular and genomic therapies. Currently, whether patients with non-reproductive cancers are male or female according to their sex chromosomes is not adequately considered in patient standard of care. This is a matter of consequence because there is growing evidence that these cancer types generally initiate earlier and are associated with higher overall incidence and rates of death in males compared with females. Gender, in contrast to sex, refers to a chosen sexual identity. Hazardous lifestyle choices (notably tobacco smoking) differ in prevalence between genders, aligned with disproportionate cancer risk. These add to underlying genetic predisposition and influences of sex steroid hormones. Together, these factors affect metabolism, immunity and inflammation, and ultimately the fidelity of the genetic code. To accurately understand how human defences against cancer erode, it is crucial to establish the influence of sex. Our Perspective highlights evidence from basic and translational research indicating that including genetic sex considerations in treatments for patients with cancer will improve outcomes. It is now time to adopt the challenge of overhauling cancer medicine based on optimized treatment strategies for females and males.
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