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基因组评估对前列腺癌风险分层、筛查及治疗的临床意义:一项叙述性综述

Clinical implications of genomic evaluations for prostate cancer risk stratification, screening, and treatment: a narrative review.

作者信息

Chung Jae-Seung, Morgan Todd M, Hong Sung Kyu

机构信息

Department of Urology, Inje University Haeundae Paik Hospital, Busan, Korea.

Department of Urology, University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA.

出版信息

Prostate Int. 2020 Sep;8(3):99-106. doi: 10.1016/j.prnil.2020.09.001. Epub 2020 Sep 14.

Abstract

New classification systems based on molecular features have been introduced to improve precision medicine for prostate cancer (PCa). This review covers the increasing risk of PCa and the differences in response to targeted therapy that are related to specific gene variations. We believe that genomic evaluations will be useful for guiding PCa risk stratification, screening, and treatment. We searched the PubMed and MEDLINE databases for articles related to genomic testing for PCa that were published in 2020 or earlier. There is increasing evidence that germline mutations in DNA repair genes, such as or , are closely related to the development and aggressiveness of PCa. Targeted prostate-specific antigen screening based on the presence of germline alterations in DNA repair genes is recommend to achieve an early diagnosis of PCa. In cases of localized PCa, even if it has a favorable risk classification, patients under active surveillance with these gene alterations are likely to develop aggressive PCa. Thus, active treatment may be preferable to active surveillance for these patients. In cases of metastatic castration-resistant PCa, and DNA mismatch repair genes may be useful biomarkers for predicting the response to androgen receptor-targeting agents, poly (ADP-ribose) polymerase inhibitors, platinum chemotherapy, prostate-specific membrane antigen-targeted therapy, immunotherapy, and radium-223. Genomic evaluations may allow for risk stratification of patients with PCa based on their molecular features, which may help guide precision medicine for treating PCa.

摘要

基于分子特征的新分类系统已被引入,以改善前列腺癌(PCa)的精准医疗。本综述涵盖了PCa风险的增加以及与特定基因变异相关的靶向治疗反应差异。我们认为基因组评估将有助于指导PCa风险分层、筛查和治疗。我们在PubMed和MEDLINE数据库中搜索了2020年或更早发表的与PCa基因组检测相关的文章。越来越多的证据表明,DNA修复基因中的种系突变,如 或 ,与PCa的发生和侵袭性密切相关。建议基于DNA修复基因种系改变的存在进行靶向前列腺特异性抗原筛查,以实现PCa的早期诊断。在局限性PCa病例中,即使其风险分类良好,对这些基因改变进行主动监测的患者也可能发展为侵袭性PCa。因此,对于这些患者,积极治疗可能比主动监测更可取。在转移性去势抵抗性PCa病例中, 和DNA错配修复基因可能是预测对雄激素受体靶向药物、聚(ADP-核糖)聚合酶抑制剂、铂类化疗、前列腺特异性膜抗原靶向治疗、免疫治疗和镭-223反应性的有用生物标志物。基因组评估可以根据PCa患者的分子特征对其进行风险分层,这可能有助于指导PCa的精准医疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d2e/7557186/dfb9e54be16f/gr1.jpg

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