Sarcoma Unit, The Royal Marsden NHS Foundation Trust, 203 Fulham Road, London SW3 6JJ, UK.
Department of Medical Oncology, University Campus Bio-Medico, 00128 Rome, Italy.
Cells. 2021 Jun 17;10(6):1533. doi: 10.3390/cells10061533.
Sarcomas are a heterogeneous group of rare malignancies originating from mesenchymal tissues with limited therapeutic options. Recently, alterations in components of the fibroblast growth factor receptor (FGFR) signaling pathway have been identified in a range of different sarcoma subtypes, most notably gastrointestinal stromal tumors, rhabdomyosarcomas, and liposarcomas. These alterations include genetic events such as translocations, mutations, and amplifications as well as transcriptional overexpression. Targeting FGFR has therefore been proposed as a novel potential therapeutic approach, also in light of the clinical activity shown by multi-target tyrosine kinase inhibitors in specific subtypes of sarcomas. Despite promising preclinical evidence, thus far, clinical trials have enrolled very few sarcoma patients and the efficacy of selective FGFR inhibitors appears relatively low. Here, we review the known alterations of the FGFR pathway in sarcoma patients as well as the preclinical and clinical evidence for the use of FGFR inhibitors in these diseases. Finally, we discuss the possible reasons behind the current clinical data and highlight the need for biomarker stratification to select patients more likely to benefit from FGFR targeted therapies.
肉瘤是一组起源于间充质组织的罕见恶性肿瘤，治疗选择有限。最近，在多种不同的肉瘤亚型中，包括胃肠道间质瘤、横纹肌肉瘤和脂肪肉瘤中，都发现了成纤维细胞生长因子受体（FGFR）信号通路成分的改变。这些改变包括遗传事件，如易位、突变和扩增以及转录过度表达。因此，靶向 FGFR 被提议作为一种新的潜在治疗方法，这也考虑到多靶点酪氨酸激酶抑制剂在特定肉瘤亚型中显示出的临床活性。尽管有有前景的临床前证据，但迄今为止，临床试验仅招募了极少数肉瘤患者，选择性 FGFR 抑制剂的疗效似乎相对较低。在这里，我们回顾了肉瘤患者 FGFR 通路的已知改变，以及 FGFR 抑制剂在这些疾病中的临床前和临床证据。最后，我们讨论了当前临床数据背后的可能原因，并强调了需要进行生物标志物分层，以选择更有可能从 FGFR 靶向治疗中获益的患者。
