Li Huan, Jiang Weibo, Liu Shui, Yang Manshi, Chen Siyuan, Pan Yihan, Cui Mengying
The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
Department of Orthopaedic, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
Mol Cell Biochem. 2024 Feb;479(2):213-231. doi: 10.1007/s11010-023-04723-1. Epub 2023 Apr 7.
Sex differences in cancer incidence and survival are constant and pronounced globally, across all races and all age groups of cancer types. In 2016, after the National Institutes of Health proposed a policy of utilizing sex as a biological variable, researchers started paying more attention to the molecular mechanisms behind gender variations in cancer. Historically, most previous studies investigating sex differences have been centered on gonadal sex hormones. Nevertheless, sex differences also involve genetic and molecular pathways that run throughout the entire process of cancer cell proliferation, metastasis, and treatment response, in addition to sex hormones. In particular, there is significant gender dimorphism in the efficacy and toxicity of oncology treatments, including conventional radiotherapy and chemotherapy, as well as the emerging targeted therapies and immunotherapy. To be clear, not all mechanisms will exhibit gender bias, and not all gender bias will affect cancer risk. Our goal in this review is to discuss some of the significant sex-related changes in fundamental cancer pathways. To this purpose, we summarize the differential impact of gender on cancer development in three dimensions: sex hormones, genetics, and epigenetics, and focus on current hot subjects including tumor suppressor function, immunology, stem cell renewal, and non-coding RNAs. Clarifying the essential mechanisms of gender differences will help guide the clinical treatment of both sexes in tumor radiation and chemotherapy, medication therapy with various targets, immunotherapy, and even drug development. We anticipate that sex-differentiated research will help advance sex-based cancer personalized medicine models and encourage future basic scientific and clinical research to take sex into account.
癌症发病率和生存率的性别差异在全球范围内、所有种族以及所有癌症类型的所有年龄组中都是持续且显著的。2016年，在美国国立卫生研究院提出将性别作为生物学变量的政策后，研究人员开始更加关注癌症中性别差异背后的分子机制。从历史上看，以往大多数研究性别差异的研究都集中在性腺性激素上。然而，除了性激素外，性别差异还涉及贯穿癌细胞增殖、转移和治疗反应全过程的遗传和分子途径。特别是，在肿瘤治疗的疗效和毒性方面存在显著的性别二态性，包括传统的放疗和化疗，以及新兴的靶向治疗和免疫治疗。需要明确的是，并非所有机制都会表现出性别偏见，也并非所有性别偏见都会影响癌症风险。我们撰写这篇综述的目的是讨论癌症基本途径中一些与性别相关的显著变化。为此，我们从性激素、遗传学和表观遗传学三个维度总结了性别对癌症发展的不同影响，并聚焦于当前的热门话题，包括肿瘤抑制功能、免疫学、干细胞更新和非编码RNA。阐明性别差异的基本机制将有助于指导肿瘤放疗和化疗、各种靶点的药物治疗、免疫治疗甚至药物研发中男女两性的临床治疗。我们预计，性别差异研究将有助于推进基于性别的癌症个性化医学模式，并鼓励未来的基础科学和临床研究考虑性别因素。
