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非裔美国人中前列腺癌的种族差异与可行的治疗思路和新型免疫疗法。

Racial disparity in prostate cancer in the African American population with actionable ideas and novel immunotherapies.

机构信息

The Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

出版信息

Cancer Rep (Hoboken). 2021 Oct;4(5):e1340. doi: 10.1002/cnr2.1340. Epub 2021 Feb 17.

Abstract

BACKGROUND

African Americans (AAs) in the United States are known to have a higher incidence and mortality for Prostate Cancer (PCa). The drivers of this epidemiological disparity are multifactorial, including socioeconomic factors leading to lifestyle and dietary issues, healthcare access problems, and potentially tumor biology.

RECENT FINDINGS

Although recent evidence suggests once access is equal, AA men have equal outcomes to Caucasian American (CA) men, differences in PCa incidence remain, and there is much to do to reverse disparities in mortality across the USA. A deeper understanding of these issues, both at the clinical and molecular level, can facilitate improved outcomes in the AA population. This review first discusses PCa oncogenesis in the context of its diverse hallmarks before benchmarking key molecular and genomic differences for PCa in AA men that have emerged in the recent literature. Studies have emphasized the importance of tumor microenvironment that contributes to both the unequal cancer burden and differences in clinical outcome between the races. Management of comorbidities like obesity, hypertension, and diabetes will provide an essential means of reducing prostate cancer incidence in AA men. Although requiring further AA specific research, several new treatment strategies such as immune checkpoint inhibitors used in combination PARP inhibitors and other emerging vaccines, including Sipuleucel-T, have demonstrated some proven efficacy.

CONCLUSION

Genomic profiling to integrate clinical and genomic data for diagnosis, prognosis, and treatment will allow physicians to plan a "Precision Medicine" approach to AA men. There is a pressing need for further research for risk stratification, which may allow early identification of AA men with higher risk disease based on their unique clinical, genomic, and immunological profiles, which can then be mapped to appropriate clinical trials. Treatment options are outlined, with a concise description of recent work in AA specific populations, detailing several targeted therapies, including immunotherapy. Also, a summary of current clinical trials involving AA men is presented, and it is important that policies are adopted to ensure that AA men are actively recruited. Although it is encouraging that many of these explore the lifestyle and educational initiatives and therapeutic interventions, there is much still work to be done to reduce incidence and mortality in AA men and equalize current racial disparities.

摘要

背景

已知美国的非裔美国人(AA)前列腺癌(PCa)的发病率和死亡率较高。造成这种流行病学差异的原因有很多,包括导致生活方式和饮食问题的社会经济因素、医疗保健获取问题以及潜在的肿瘤生物学问题。

最近的发现

尽管最近的证据表明,一旦获得平等的机会,AA 男性与白种美国男性(CA)的结果就相等,但 PCa 的发病率仍存在差异,要在美国消除死亡率方面的种族差异还有很多工作要做。在临床和分子水平上更深入地了解这些问题,可以促进 AA 人群的治疗效果得到改善。这篇综述首先讨论了 PCa 在其多种特征的背景下的发生机制,然后为最近文献中出现的 AA 男性 PCa 的关键分子和基因组差异设定了基准。研究强调了肿瘤微环境的重要性,它导致了不同种族之间癌症负担的不平等和临床结果的差异。管理肥胖症、高血压和糖尿病等合并症将为降低 AA 男性的前列腺癌发病率提供重要手段。尽管需要进一步针对 AA 人群的研究,但几种新的治疗策略,如免疫检查点抑制剂与 PARP 抑制剂联合使用以及其他新疫苗,包括 Sipuleucel-T,已证明具有一定的疗效。

结论

基因组分析将临床和基因组数据整合在一起,用于诊断、预后和治疗,将使医生能够为 AA 男性制定“精准医学”方法。迫切需要进行进一步的风险分层研究,这可能使我们能够根据 AA 男性独特的临床、基因组和免疫特征,早期识别出疾病风险较高的人群,然后将这些特征映射到适当的临床试验中。本文概述了治疗选择,并简要描述了针对 AA 特定人群的最新工作,详细介绍了几种靶向治疗方法,包括免疫疗法。此外,还介绍了目前涉及 AA 男性的临床试验摘要,重要的是要采取政策确保积极招募 AA 男性。尽管令人鼓舞的是,其中许多研究都探讨了生活方式和教育倡议以及治疗干预措施,但要降低 AA 男性的发病率和死亡率并平等化当前的种族差异,仍有许多工作要做。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0aa/8551995/9aefc8eac5d0/CNR2-4-e1340-g002.jpg

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