The fibroblast growth factor receptor (FGFR) signaling pathway has long been known to cancer researchers because of its role in cell survival, proliferation, migration, and angiogenesis. Dysregulation of FGFR signaling is frequently reported in cancer studies, but most of these studies focus on FGFR1-3. However, there is growing evidence implicating an important and unique role of FGFR4 in oncogenesis, tumor progression, and resistance to anti-tumor therapy in multiple types of cancer. Importantly, there are several novel FGFR4-specific inhibitors in clinical trials, making FGFR4 an attractive target for further research. In this review, we focus on assessing the role of FGFR4 in cancer, with an emphasis on breast cancer. First, the structure, physiological functions and downstream signaling pathways of FGFR4 are introduced. Next, different mechanisms reported to cause aberrant FGFR4 activation and their functions in cancer are discussed, including FGFR4 overexpression, FGF ligand overexpression, FGFR4 somatic hotspot mutations, and the FGFR4 G388R single nucleotide polymorphism. Finally, ongoing and recently completed clinical trials targeting FGFRs in cancer are reviewed, highlighting the therapeutic potential of FGFR4 inhibition for the treatment of breast cancer.

成纤维细胞生长因子受体 (FGFR) 信号通路因其在细胞存活、增殖、迁移和血管生成中的作用而早已为癌症研究人员所知。癌症研究中经常报道 FGFR 信号传导失调，但大多数研究都集中在 FGFR1-3。然而，越来越多的证据表明 FGFR4 在多种癌症的肿瘤发生、肿瘤进展和抗肿瘤治疗耐药性中发挥着重要而独特的作用。重要的是，有几种新型 FGFR4 特异性抑制剂正在临床试验中，这使得 FGFR4 成为进一步研究的有吸引力的目标。在这篇综述中，我们重点评估 FGFR4 在癌症中的作用，重点是乳腺癌。首先介绍了FGFR4的结构、生理功能及下游信号通路。接下来，讨论了导致 FGFR4 异常激活的不同机制及其在癌症中的功能，包括 FGFR4 过表达、FGF 配体过表达、FGFR4 体细胞热点突变和 FGFR4 G388R 单核苷酸多态性。最后，对正在进行和最近完成的针对癌症中 FGFR 的临床试验进行了回顾，强调了 FGFR4 抑制治疗乳腺癌的治疗潜力。