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膀胱癌和肾癌的生物标志物导向治疗。

Biomarker-Oriented Therapy in Bladder and Renal Cancer.

机构信息

Department of Urology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.

Department of Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.

出版信息

Int J Mol Sci. 2021 Mar 11;22(6):2832. doi: 10.3390/ijms22062832.

Abstract

Treatment of patients with urothelial carcinoma (UC) of the bladder or renal cancer has changed significantly during recent years and efforts towards biomarker-directed therapy are being investigated. Immune checkpoint inhibition (ICI) or fibroblast growth factor receptor (FGFR) directed therapy are being evaluated for non-muscle invasive bladder cancer (NMIBC) patients, as well as muscle-invasive bladder cancer (MIBC) patients. Meanwhile, efforts to predict tumor response to neoadjuvant chemotherapy (NAC) are still ongoing, and genomic biomarkers are being evaluated in prospective clinical trials. Currently, patients with metastatic UC (mUC) are usually treated with second-line ICI, while cisplatin-ineligible patients with programmed death-ligand 1 (PD-L1) positive tumors can benefit from first-line ICI. Platinum-relapsed UC patients harboring FGFR2/3 mutations can be treated with erdafitinib, while enfortumab vedotin has emerged as a novel third-line treatment option for mUC. In metastatic (clear cell) renal cell carcinoma (RCC), ICI was first introduced as second-line treatment after vascular endothelial growth factor receptor-tyrosine kinase inhibition (VEGFR-TKI). Currently, ICIs have also been introduced as first-line treatment in metastatic RCC. Although there is no evidence up to now for beneficial adjuvant treatment after surgery with VEGFR-TKIs in high-risk non-metastatic RCC, several trials are underway investigating the potential beneficial effect of ICIs in this setting.

摘要

近年来,治疗膀胱癌或肾癌的患者的方法发生了重大变化,目前正在研究针对生物标志物的治疗方法。免疫检查点抑制剂(ICI)或成纤维细胞生长因子受体(FGFR)靶向治疗正在评估非肌肉浸润性膀胱癌(NMIBC)患者以及肌肉浸润性膀胱癌(MIBC)患者。同时,预测肿瘤对新辅助化疗(NAC)反应的努力仍在进行中,正在前瞻性临床试验中评估基因组生物标志物。目前,转移性膀胱癌(mUC)患者通常接受二线 ICI 治疗,而程序性死亡配体 1(PD-L1)阳性肿瘤且不符合顺铂条件的患者可以从一线 ICI 中获益。携带 FGFR2/3 突变的铂类复发 UC 患者可以用厄达替尼治疗,而恩福替尼单抗已经成为转移性 UC 的新三线治疗选择。在转移性(透明细胞)肾细胞癌(RCC)中,ICI 最初作为血管内皮生长因子受体酪氨酸激酶抑制剂(VEGFR-TKI)的二线治疗药物。目前,ICI 也已被引入转移性 RCC 的一线治疗。尽管迄今为止,在高风险非转移性 RCC 中,手术后使用 VEGFR-TKI 进行辅助治疗没有证据表明有益,但正在进行几项试验以研究在这种情况下使用 ICI 的潜在有益效果。

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