Therapeutic options for metastatic bladder cancer (BC) have seen minimal evolution over the past 30 years, with platinum-based chemotherapy remaining the mainstay of standard of care for metastatic BC. Recently, five immune checkpoint inhibitors (ICIs) have been approved by the FDA as second-line therapy, and two ICIs are approved as first-line treatment in selected patients. Molecular alterations of muscle-invasive bladder cancer (MIBC) have been reported by The Cancer Genome Atlas. About 15% of patients with MIBC have molecular alterations in the fibroblast growth factor (FGF) axis. Several ongoing trials are testing novel FGF receptor (FGFR) inhibitors in patients with FGFR genomic aberrations. Recently, erdafitinib, a pan-FGFR inhibitor, was approved by the FDA in patients with metastatic BC who have progressed on platinum-based chemotherapy. We reviewed the literature over the last decade and provide a summary of current knowledge of FGF signaling, and the prognosis associated with FGFR mutations in BC. We cover the role of FGFR inhibition with non-selective and selective tyrosine kinase inhibitors as well as novel agents in metastatic BC. Efficacy and safety data including insights from mechanism-based toxicity are reported for selected populations of metastatic BC with FGFR aberrations. Current strategies to managing resistance to anti-FGFR agents is addressed, and the importance of developing reliable biomarkers as the therapeutic landscape moves towards an individualized therapeutic approach.

中文翻译：

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膀胱癌治疗的未来：优化对成纤维细胞生长因子受体的抑制作用。

在过去的30年中，转移性膀胱癌（BC）的治疗选择几乎没有进展，铂类化学疗法仍是转移性BC的标准护理方法。最近，五种免疫检查点抑制剂（ICI）已被FDA批准为二线治疗药物，而两种ICI被批准为某些患者的一线治疗药物。癌症基因组图谱已经报道了肌肉浸润性膀胱癌（MIBC）的分子改变。大约15％的MIBC患者在成纤维细胞生长因子（FGF）轴上具有分子改变。数项正在进行的试验正在对具有FGFR基因组异常的患者测试新型FGF受体（FGFR）抑制剂。最近，FDA批准了泛FGFR抑制剂erdafitinib用于已接受铂类化学疗法治疗的转移性BC患者。我们回顾了过去十年的文献，并提供了有关FGF信号传导的最新知识以及与BC中FGFR突变相关的预后的摘要。我们涵盖了非选择性和选择性酪氨酸激酶抑制剂以及转移性BC中的新型药物对FGFR抑制的作用。报告了针对某些具有FGFR畸变的转移性BC人群的功效和安全性数据，包括基于机制毒性的见解。提出了管理抗FGFR药物耐药性的当前策略，并且随着治疗趋势朝着个体化治疗方法发展可靠的生物标记物的重要性。我们涵盖了非选择性和选择性酪氨酸激酶抑制剂以及转移性BC中的新型药物对FGFR抑制的作用。报告了针对某些具有FGFR畸变的转移性BC人群的功效和安全性数据，包括基于机制毒性的见解。提出了管理抗FGFR药物耐药性的当前策略，并且随着治疗趋势朝着个体化治疗方法发展可靠的生物标记物的重要性。我们涵盖了非选择性和选择性酪氨酸激酶抑制剂以及转移性BC中的新型药物对FGFR抑制的作用。报告了针对某些具有FGFR畸变的转移性BC人群的功效和安全性数据，包括基于机制毒性的见解。提出了管理抗FGFR药物耐药性的当前策略，并且随着治疗趋势朝着个体化治疗方法发展可靠的生物标记物的重要性。