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肌层浸润性膀胱癌药物研发的不同阶段。

Different stages in drug development for muscle-invasive bladder cancer.

作者信息

Ineichen Gallus Beatus, Röthlisberger Raphael, Johner Kevin Fabian, Seiler Roland

机构信息

Department of Urology, University of Bern, Bern, Switzerland.

出版信息

Transl Androl Urol. 2017 Dec;6(6):1060-1066. doi: 10.21037/tau.2017.11.22.

Abstract

Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease. Despite optimal therapy, half of the patients will succumb to disease. This prognosis could not be improved over the last three decades. Therefore, MIBC is left behind from other cancers such as prostate, where novel treatment options were discovered and improve patient outcomes. While being aware of the recent emerging evidence of checkpoint inhibition in MIBC, we aim to describe different stages of drug development in MIBC by using three specific targets. On the example of Her2 targeting, we aimed to indicate, that either a target is ineffective in MIBC or that the patient selection is insufficient. The first clinical trials using a pan fibroblast growth factor receptor (panFGFR) inhibitor to target the FGFR pathway showed promising results. Data of further trials are to be awaited before implementing these drugs into daily clinical practice. A large variety of novel agents are investigated and . On the example of a malaria protein, we aimed to discuss a treatment paradigm that is not dependent on pathway signaling and the genomic landscape of MIBC. The ultimate question still remains to be answered: How do we select the optimal treatment for the right patient?

摘要

肌肉浸润性膀胱癌(MIBC)是一种侵袭性很强的疾病。尽管进行了最佳治疗,仍有一半的患者会死于该病。在过去三十年里,这种预后情况并未得到改善。因此,MIBC在癌症治疗方面落后于其他癌症,比如前列腺癌,后者已经发现了新的治疗方案并改善了患者的治疗效果。虽然我们已经了解到MIBC中检查点抑制的最新证据,但我们旨在通过三个特定靶点来描述MIBC药物开发的不同阶段。以针对Her2靶点为例,我们旨在表明,要么该靶点在MIBC中无效,要么患者选择不充分。首个使用泛成纤维细胞生长因子受体(panFGFR)抑制剂靶向FGFR通路的临床试验显示出了有前景的结果。在将这些药物应用于日常临床实践之前,还需等待进一步试验的数据。目前正在研究各种各样的新型药物。以一种疟疾蛋白为例,我们旨在探讨一种不依赖于通路信号传导和MIBC基因组格局的治疗模式。最终的问题仍然有待解答:我们如何为合适的患者选择最佳治疗方案?

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Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.
Cell. 2017 Oct 19;171(3):540-556.e25. doi: 10.1016/j.cell.2017.09.007. Epub 2017 Oct 5.
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