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[泌尿系统癌症的精准肿瘤学治疗选择]

[Precision oncology options in urological cancers].

作者信息

Franz Antonia, Plage Henning, Fendler Annika, Schlomm Thorsten, Kornienko Kira

机构信息

Klinik für Urologie, Charité - Universitätsmedizin Berlin, Charité Platz 1, 10117, Berlin, Deutschland.

出版信息

Urologie. 2023 Jul;62(7):696-704. doi: 10.1007/s00120-023-02119-z. Epub 2023 Jun 9.

Abstract

Advancements in the molecular genetic understanding of urological tumors have enabled the identification of numerous new therapeutic targets. Based on routinely applicable tumor sequencing, individual treatment decisions have been introduced in the context of precision oncology. This work provides an overview of the latest targeted tumor therapies in the treatment of prostate cancer, urothelial carcinoma, and renal cell carcinoma. Current studies on the administration of FGFR-inhibitors ("fibroblast growth factor receptor") in metastatic urothelial carcinoma show a high tumor response in patients with selected FGFR alterations. PARP-inhibitors ("Poly-[ADP-Ribose-]Polymerase") are routinely used in the treatment of metastatic prostate cancer. Patients with a BRCA mutation ("BReast CAncer gene") show high radiological response rates. Moreover, we discuss the latest results of the combination of PARP inhibitors with novel androgen receptor pathway inhibitors. In metastatic prostate cancer, there are numerous ongoing studies evaluating the promising drug targets PI3K/AKT/mTOR ("Phosphatidylinositol-3-Kinase")/AKT/mTOR ("mammalian target of rapamycine") and VEGF signaling pathways ("vascular endothelial growth factor"). A HIF-2a inhibitor ("hypoxia inducible factor") offers a promising new therapeutic option for metastatic renal cell carcinoma. Overall, molecular diagnostics to determine the right therapy for the right patient subgroup at the right time is important for uro-oncological precision medicine.

摘要

对泌尿系统肿瘤分子遗传学认识的进展,使得众多新的治疗靶点得以确定。基于常规适用的肿瘤测序,在精准肿瘤学背景下引入了个体化治疗决策。本文综述了前列腺癌、尿路上皮癌和肾细胞癌治疗中最新的靶向肿瘤治疗方法。目前关于在转移性尿路上皮癌中应用FGFR抑制剂(“成纤维细胞生长因子受体”)的研究表明,在具有特定FGFR改变的患者中肿瘤反应率较高。PARP抑制剂(“聚[ADP-核糖]聚合酶”)常规用于转移性前列腺癌的治疗。具有BRCA突变(“乳腺癌基因”)的患者显示出较高的放射学反应率。此外,我们还讨论了PARP抑制剂与新型雄激素受体途径抑制剂联合应用的最新结果。在转移性前列腺癌中,有许多正在进行的研究评估有前景的药物靶点PI3K/AKT/mTOR(“磷脂酰肌醇-3-激酶”)/AKT/mTOR(“雷帕霉素哺乳动物靶点”)和VEGF信号通路(“血管内皮生长因子”)。HIF-2α抑制剂(“缺氧诱导因子”)为转移性肾细胞癌提供了一种有前景的新治疗选择。总体而言,分子诊断对于在正确的时间为正确的患者亚组确定正确的治疗方法,对泌尿肿瘤精准医学至关重要。

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