Costa Ricardo, Carneiro Benedito A, Taxter Timothy, Tavora Fabio A, Kalyan Aparna, Pai Sachin A, Chae Young Kwang, Giles Francis J
Developmental Therapeutics Program, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
Oncotarget. 2016 Aug 23;7(34):55924-55938. doi: 10.18632/oncotarget.10482.
Fibroblast growth factor receptors (FGFR) are transmembrane kinase proteins with growing importance in cancer biology given the frequency of molecular alterations and vast interface with multiple other signaling pathways. Furthermore, numerous FGFR inhibitors in clinical development demonstrate the expanding therapeutic relevance of this pathway. Indeed, results from early phase clinical trials already indicate that a subset of patients with advanced tumors derive benefit from FGFR targeted therapies. FGFR gene aberrations and FGFR gene rearrangements are relatively rare in solid malignancies. The recently described FGFR3-TACC3 fusion protein has a constitutively active tyrosine kinase domain and promotes aneuploidy. We summarize the prevalence data on FGFR3-TACC3 fusions among different histological tumor types and the preliminary evidence that this rearrangement represents a targetable molecular aberration in some patients with solid tumors.
成纤维细胞生长因子受体(FGFR)是跨膜激酶蛋白,鉴于其分子改变的频率以及与多种其他信号通路的广泛联系,在癌症生物学中的重要性日益增加。此外,众多处于临床开发阶段的FGFR抑制剂表明了该信号通路在治疗方面的相关性不断扩大。事实上,早期临床试验结果已表明,一部分晚期肿瘤患者可从FGFR靶向治疗中获益。FGFR基因畸变和FGFR基因重排在实体恶性肿瘤中相对少见。最近描述的FGFR3-TACC3融合蛋白具有组成型活性酪氨酸激酶结构域,并促进非整倍体形成。我们总结了不同组织学肿瘤类型中FGFR3-TACC3融合的流行率数据,以及该重排在一些实体瘤患者中代表可靶向分子畸变的初步证据。