成纤维细胞生长因子受体-癌症治疗新靶点

成纤维细胞生长因子(FGFs)通过作用于其受体(成纤维细胞生长因子受体,FGFRs)在许多生理过程中发挥重要作用,如胚胎形成、创伤修复、血管生成等。近年来,越来越多的证据表明FGFRs是某些癌症的驱动基因,并且以"细胞自治"的方式维持肿瘤细胞的恶性特征,通过诱导促有丝分裂和生存信号、促进肿瘤细胞侵袭转移、促进上皮间质转化、促进血管生成及参与肿瘤复发耐药作用作为癌基因参与肿瘤发生发展进程的多重步骤,但也有研究证实FGFR信号在某些肿瘤类型中具有抑制肿瘤的功能。这些研究结果使得FGFRs成为越来越具有吸引力的癌症治疗新靶点。本文阐述了FGFRs信号通路在多种肿瘤中的作用,并且对处于研发或试验阶段的抗FGFRs药物(包括小分子酪氨酸激酶抑制剂和单克隆抗体)进行了概括。

Fibroblast Growth Factor Receptors:A New Therapeutic Targets in Cancer

Fibroblast growth factors (FGFs) acting through their cognate receptors (FGFRs) play vital roles in many physiologic processes, including embryogenesis, wound healing, angiogenesis and so on. Studies in the last few years have uncovered increasing evidence that FGFRs are driving oncogenes in certain cancers and act in a cell autonomous fashion to maintain the malignant properties of tumour cells,and promote multiple steps of cancer progression by inducing mitogenic and survival signals, promoting epithelial-mesenchymal transformation, invasion, metastasis and tumour angiogenesis, as well as participating in treatment resistance and tumor recurrence, but there is unequivocal evidence for a tumour suppressive role of FGFR in some tumors.In this article, we describe the role of FGFRs in various tumours, and summarize the range of agents currently employed or in development to antagonise FGFRs, including small molecule tyrosine kinase inhibitors and monoclonal antibodies.