Mancini Francesca, Giorgini Ludovica, Teveroni Emanuela, Pontecorvi Alfredo, Moretti Fabiola
Research Unit on Human Reproduction, International Scientific Institute Paul VI, Fondazione Policlinico A. Gemelli, IRCCS, Rome, Italy.
Institute of Biochemistry and Cell Biology, National Research Council of Italy, Monterotondo, Italy.
Front Oncol. 2021 Jul 8;11:698946. doi: 10.3389/fonc.2021.698946. eCollection 2021.
Sex profoundly affects cancer incidence and susceptibility to therapy, with sex hormones highly contributing to this disparity. Various studies and omics data suggest a relationship between sex and the oncosuppressor p53 circuitry, including its regulators MDM2 and MDM4. Association of this network with genetic variation underlies sex-related altered cancer risk, age of onset, and cancer sensitivity to therapy. Moreover, sex-related factors, mainly estrogenic hormones, can affect the levels and/or function of the p53 network both in hormone-dependent and independent cancer. Despite this evidence, preclinical and clinical studies aimed to evaluate p53 targeted therapy rarely consider sex and related factors. This review summarizes the studies reporting the relationship between sex and the p53 circuitry, including its associated regulators, MDM2 and MDM4, with particular emphasis on estrogenic hormones. Moreover, we reviewed the evaluation of sex/hormone in preclinical studies and clinical trials employing p53-target therapies, and discuss how patients' sex and hormonal status could impact these therapeutic approaches.
性别对癌症发病率和治疗易感性有深远影响，性激素在这种差异中起很大作用。各种研究和组学数据表明，性别与肿瘤抑制因子p53信号通路之间存在关联，包括其调节因子MDM2和MDM4。该网络与基因变异的关联是性别相关的癌症风险、发病年龄和癌症治疗敏感性改变的基础。此外，与性别相关的因素，主要是雌激素，可在激素依赖性和非依赖性癌症中影响p53网络的水平和/或功能。尽管有这些证据，但旨在评估p53靶向治疗的临床前和临床研究很少考虑性别及相关因素。本综述总结了报告性别与p53信号通路（包括其相关调节因子MDM2和MDM4）之间关系的研究，特别强调雌激素。此外，我们回顾了在采用p53靶向治疗的临床前研究和临床试验中对性别/激素的评估，并讨论了患者的性别和激素状态如何影响这些治疗方法。
