Role of Sex in the Therapeutic Targeting of p53 Circuitry

被引：2

作者：

Mancini, Francesca ^{[1
]}

Giorgini, Ludovica ^{[2
,3
]}

Teveroni, Emanuela ^{[1
]}

Pontecorvi, Alfredo ^{[3
]}

Moretti, Fabiola ^{[2
]}

机构：

[1] IRCCS, Res Unit Human Reprod, Int Sci Inst Paul VI, Fdn Policlin A Gemelli, Rome, Italy

[2] Natl Res Council Italy, Inst Biochem & Cell Biol, Monterotondo, Italy

[3] Catholic Univ Sacred Heart Rome, Fdn Policlin A Gemelli, IRCCS, Rome, Italy

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 11卷

关键词：

cancer therapy; p53; sex; estrogen; MDM2; MDM4; ESTROGEN-RECEPTOR-ALPHA; SINGLE NUCLEOTIDE POLYMORPHISM; PHASE-I TRIAL; NON-HDM2-MEDIATED PEPTIDE INHIBITOR; ACCELERATES TUMOR-FORMATION; MDM4; SNP34091; RS4245739; GENOME-WIDE ASSOCIATION; BREAST-CANCER; MAMMARY EPITHELIUM; OVARIAN-CANCER;

D O I：

10.3389/fonc.2021.698946

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：11

共 117 条

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