These studies provide the first direct evidence for both the involvement of the FGFR1 V561M mutation and PTEN inactivation in the development of resistance in leukemias overexpressing chimeric FGFR1. These studies also provide a potential strategy to treat leukemias and lymphomas driven by FGFR1 activation that become resistant to FGFR1 inhibitors.

There are four identified FGFR receptors, FGFR1, FGFR2, FGFR3, and FGFR4 that bind to a variety of FGFs. Twenty-two different FGFs have also been identified. FGF1 through FGF10 all bind to FGFRs. FGF11 through FGF14 have similar homologies to the other FGFs, but do not bind to FGFRs and have distinct functional differences.

2020年10月20日 · Treatment with different tyrosine kinase inhibitors (TKIs) revealed that, in both FGFR1 mutation and Pten deletion-mediated resistance, sustained Akt activation in resistant cells leads to...

In FGFR-driven leukemia, the activation mutation V561M within the FGFR1 tyrosine kinase domain, coupled with inactivation of PTEN, led to increased PI3K/AKT activity and acquired resistance to...

2019年9月3日 · PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression were evaluated by immunohistochemistry (IHC). Expression level was classified as tumor cells (TC) 3 (≥ 50%), TC2 (5-49%), TC1 (1-4%), or TC0 (< 1%), and as tumor-infiltrating immune cells (IC) 3 (≥ 50%), IC2 (5-49%), IC1 (1-4%), or IC0 (< 1%) for PD-L1.

fgfr1激酶结构域中激活的v561m突变和pten的突变失活导致pi3k / akt活性增加。 PTEN突变细胞中PTEN的异位表达使它们对FGFR抑制剂重新敏感。 用BGJ398与BEZ235 PI3K抑制剂联合治疗耐药细胞，可显示出对体外生长的累加效应，并延长了异种移植体内模型的存活时间。

目的：纤维母细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)基因扩增是目前肺鳞癌中最具有发展潜力药物分子靶点之一.目前,多个FGFR1抑制剂的临床试验正在进行中,如AZD4547、BGJ398、LY2874455等.但中国肺鳞癌患者中FGFR1基因扩增的发生频率及临床意义 …

2024年5月23日 · CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 and sensitized PTEN-deficient prostate cancer to the AKT inhibitor capivasertib. This study reveals the role of KLF5 acetylation in reprogramming CAFs and provides a rationale for combined therapies using inhibitors of AKT and CX3CR1.

In the present report, two unique mechanisms for resistance were identified in FGFR1-resistant cell lines, one involving an activating mutation in FGFR1 and the second mutational inactivation of PTEN, with upregulation of PI3K signaling.

Background: Fibroblast Growth Factor 20 (FGF20)-FGF receptor 1 (FGFR1) signaling is essential for cochlear hair cell (HC) and supporting cell (SC) differentiation. In other organ systems, FGFR1 signals through several intracellular pathways including MAPK (ERK), PI3K, phospholipase C ɣ (PLCɣ), and p38.