历史上，为了保护未出生的婴儿免受潜在危害，妇女经常被排除在临床试验和药物使用之外。因此，性别和性别对肿瘤生物学和临床结果的影响被大大低估了。虽然它们相互关联并经常可互换使用，但性别和性别并不是等同的概念。性别是定义物种的生物属性，根据它们的染色体构成和生殖器官，而性别则指所选择的性别认同。性别二态性很少被考虑，无论是在临床前还是临床研究中，对于性别或性别差异导致的临床结局的不足分析仍然很普遍，反映了我们针对大多数目标人群知识的差距。对于研究设计和分析中基于性别的差异的低估必然导致为男性和女性都提供“一种药物”的治疗方案。对于结直肠癌（CRC）患者，性别也会影响疾病发病率、临床病理学特征、治疗结局和耐受性。尽管全球CRC的发病率在男性中更高，但在女性中，表现右侧肿瘤和BRAF突变的患者比例更高。关于治疗效果和毒性的性别相关差异，药物剂量没有考虑性别特异性的药代动力学差异。与结直肠癌有关的5-氟尿嘧啶、靶向治疗和免疫治疗的毒性被报道为女性比男性更普遍，尽管关于治疗效果的差异的证据更具争议性。本文旨在概述目前关于癌症性别和性别差异研究的进展，并总结有关CRC中性别和性别视角的日益增长的文献，以及它们对肿瘤生物学、治疗效果和毒性的影响。我们提出支持研究如何将生物性别和性别影响CRC作为精准肿瘤学的附加价值。版权所有©2023年作者。由Elsevier Ltd.出版。保留所有权利。

Historically women were frequently excluded from clinical trials and drug usage to protect unborn babies from potential harm. As a consequence, the impact of sex and gender on both tumour biology and clinical outcomes has been largely underestimated. Although interrelated and often used interchangeably, sex and gender are not equivalent concepts. Sex is a biological attribute that defines species according to their chromosomal makeup and reproductive organ, while gender refers to a chosen sexual identity. Sex dimorphisms are rarely taken into account, in either preclinical or clinical research, with inadequate analysis of differences in outcomes according to sex or gender still widespread, reflecting a gap in our knowledge for a large proportion of the target population. Underestimation of sex-based differences in study design and analyses has invariably led to 'one-drug' treatment regimens for both males and females. For patients with colorectal cancer (CRC), sex also has an impact on the disease incidence, clinicopathological features, therapeutic outcomes, and tolerability to anticancer treatments. Although the global incidence of CRC is higher in male subjects, the proportion of patients presenting right-sided tumours and BRAF mutations is higher among females. Concerning sex-related differences in treatment efficacy and toxicity, drug dosage does not take into account sex-specific differences in pharmacokinetics. Toxicity associated with fluoropyrimidines, targeted therapies, and immunotherapies has been reported to be more extensive for females with CRC than for males, although evidence about differences in efficacy is more controversial. This article aims to provide an overview of the research achieved so far into sex and gender differences in cancer and summarize the growing body of literature illustrating the sex and gender perspective in CRC and their impact in relation to tumour biology and treatment efficacy and toxicity. We propose endorsing research on how biological sex and gender influence CRC as an added value for precision oncology.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.