靶向膀胱癌:突变与预后方面的性别敏感视角

Targeting bladder cancer: A sex sensitive perspective in mutations and outcomes.

作者信息

Isali Ilaha, Khooblall Prajit, Helstrom Emma, Bukavina Laura

机构信息

Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH.

Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.

出版信息

Urol Oncol. 2023 Jun 20. doi: 10.1016/j.urolonc.2023.05.008.

Abstract

The incidence of bladder cancer (BC) is more common in males, however, the clinical outcome for females tends to be more unfavorable, as demonstrated by a 21% increase in mortality compared to males within two years of diagnosis. While it was previously believed that the differences in outcome were solely the result of differences in sex chromosomes and hormones, it is now acknowledged that a more intricate interplay of factors is at play. By acquiring a more comprehensive understanding of these sex-specific effects, future efforts in precision medicine can be customized to an individual's biological sex. This narrative review aims to summarize our knowledge of the molecular classification of sex differences in BC by compiling the existing evidence on genetic disparities between males and females and evaluating these disparities in both noninvasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). Our findings emphasize the significance of considering sex as a factor in future clinical trials and registry studies due to established differences in immune composition, molecular profiling, and genetic mutations between males and females. Further investigation into the molecular processes involved in the evasion or resistance of immune-based therapies, such as Bacillus Calmette-Guérin and other immunotherapies, is essential to identify markers of response or resistance that vary between male and female patients. This will aid in optimizing treatment and promoting equitable outcomes, particularly in NMIBC cases.

摘要

膀胱癌(BC)的发病率在男性中更为常见,然而,女性的临床结局往往更不理想,诊断后两年内女性死亡率比男性高出21%就证明了这一点。虽然以前认为结局差异完全是性染色体和激素差异的结果,但现在人们认识到有更复杂的因素相互作用在起作用。通过更全面地了解这些性别特异性影响,未来精准医学的努力可以根据个体的生物学性别进行定制。这篇叙述性综述旨在通过汇编关于男性和女性之间遗传差异的现有证据,并评估非侵入性膀胱癌(NMIBC)和肌肉浸润性膀胱癌(MIBC)中的这些差异,总结我们对BC性别差异分子分类的认识。我们的研究结果强调,由于男性和女性在免疫组成、分子谱和基因突变方面已确定存在差异,因此在未来的临床试验和登记研究中应将性别作为一个因素加以考虑。进一步研究卡介苗和其他免疫疗法等基于免疫的疗法逃避或抵抗所涉及的分子过程,对于识别男性和女性患者之间不同的反应或抵抗标志物至关重要。这将有助于优化治疗并促进公平的结局,特别是在NMIBC病例中。

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