FGFR2 fusion proteins drive oncogenic transformation of mouse liver organoids towards cholangiocarcinoma J Hepatol. 2021 Mar 16;S0168-8278 (21)00172-0. doi: 10.1016/j.jhep.2021.02.032. Online ahead of print FGFR2 fusions occur in 13.6% of intrahepatic cholangiocarcinoma. The expression pattern of these fusions in association with sensitivity to FGFR inhibitors warrant a new molecular classification of cholangiocarcinoma and suggest a new therapeutic approach to the disease. FGFR2 fusions occur in 13.6% of intrahepatic cholangiocarcinoma FGFR2 fusions in Intrahepatic Cholangiocarcinoma (iCCA) | FGFRscience.com Every tumor has a story. In intrahepatic cholangiocarcinoma (iCCA), it may begin with FGFR2 fusion . Alterations include point mutations, gene amplifications, and chromosomal rearrangements that may result in fusion proteins, including FGFR2 fusions. 4 In iCCA, FGFR2 fusions have been identified as key oncogenic drivers in 10% to 16% of patients 7- One patient with a novel FGFR2 fusion had clinical benefit from an in FGFR fusions were detected by using comprehensive genomic profiling in 0.2% of NSCLCs; they occurred primarily in the absence of other known driver alterations, or in a subset of cases, as likely mechanisms of acquired resistance
PEMAZYRE ® is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test FGFR2-AHCYL1 Fusion is present in 0.07% of AACR GENIE cases, with adenocarcinoma of unknown primary, cholangiocarcinoma, intrahepatic cholangiocarcinoma, adenocarcinoma of the gastroesophageal junction, and breast invasive ductal carcinoma having the greatest prevalence [ 4 ]. Top Disease Cases with FGFR2-AHCYL1 Fusion Intrahepatic cholangiocarcinoma (iCCA) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. By performing RNA- and exome-sequencing analyses, we report a novel fusion event, FGFR2-PPHLN1 (16%), and damaging mutations in the ARAF oncogene (11%). Here we demonstrate that
FGFR2 fusion proteins July 14, 2021 Dr. Mo Ebrahimkhani and colleague publish editorial in Journal of Hepatology [vc_row] [vc_column] [vc_column_text]Dr. Ebrahimkhani published an editorial in the Journal of Hepatology, entitled, Build to understand biliary oncogenesis via organoids and FGFR2 Derazantinib demonstrated encouraging anti-tumour activity and a manageable safety profile in patients with advanced, unresectable iCCA with FGFR2 fusion who progressed after chemotherapy. A pivotal trial of derazantinib in iCCA is ongoing (NCT03230318) According to the updated findings of this single-arm, multicenter study in 108 pretreated advanced CCA with FGFR2 fusion or rearrangement, infigratinib showed an overall response rate (ORR) of 23.1%, with a median duration of response of 5.0 months and median PFS of 7.3 months Substudy 1: FGFR2 fusion status based on the following assessments: a) If central laboratory designated by Sponsor: Positive FISH test; and/or b) If non-central laboratory: i) Positive FISH or NGS test: patients may be enrolled and may start dosing, but central confirmation is required* ii) Negative FISH or NGS test: tissue may be submitted to.
Particularly in ICC, chromosomal translocations involving Fibroblast Growth Factor Receptor 2 (FGFR2) have been frequently identified, resulting in the creation of oncogenic fusion proteins FGFR2 fusions occur at highest frequency in intrahepatic cholangiocarcinoma (iCCA), observed in 10-16% of patients. This lab-developed test uses a break-apart FISH probe to detect the presence of FGFR2 fusions (translocations). Fusion partners of FGFR2 are not specifically identified. As a reminder, FGFR2 CDx Molecular Analysis remains the. This test is an FDA-approved assay for the evaluation of somatic mutations and fusions in the FGFR3 and FGFR2 genes to identify urothelial carcinoma patients that may be eligible for treatment with FGFR-targeted therapies such as Balversa (erdafitinib).. This test uses targeted reverse transcriptase (RT)-PCR to evaluate for somatic mutations within the FGFR3 gene: R248C, S249C, G370C, and Y373C Fibroblast growth factor receptor 2 (FGFR2) fusions belong to the most frequent and therapeutically relevant alterations in ICC, and the first FGFR inhibitor was recently approved for the treatment of patients with progressed, fusion-positive ICC Background & Aims. About 15% of intrahepatic cholangiocarcinomas (iCCAs) express fibroblast growth factor receptor 2 (FGFR2) fusion proteins (FFs), usually alongside mutational inactivation of TP53, CDKN2A or BAP1.In FFs, FGFR2 residues 1-768 fuse to sequences encoded by a diverse array of partner genes (>60) causing oncogenic FF activation
FGFR2 mutations are associated with craniosynostosis syndromes, which are skull malformations caused by premature fusion of cranial sutures and other disease features according to the mutation itself. Analysis of chromosomal anomalies in patients led to the identification and confirmation of FGFR2 as a cleft lip and/or palate locus The FGFR2 gene provides instructions for making a protein called fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factor receptors are related proteins that are involved in important processes such as cell growth and division (proliferation), cell maturation (differentiation), bone development, formation of blood vessels (angiogenesis), wound healing, and embryonic development.
FGFR2-ACSL5 fusion is associated with resistance to LY2874455 in FGFR2-amplified gastric cancer . FGFR2 mutation is associated with endometrial carcinoma progression and abdominopelvic metastasis. FGFR inhibitors, particularly BGJ398, are therapeutic options for cholangiocarcinoma patients harboring FGFR2-CCDC6 fusions In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer with a FGFR2 fusion gene, worsening after cancer chemotherapy. In Europe , Pemazyre is approved for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or rearrangement that have progressed after at. Data from cohort 1 provided proof of concept for derazantinib monotherapy in patients with FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. As such, cohort 2 of the trial is examining..
FGF2 / bFGF Protein Tissue Culture & GMP Grade Available. Industry Leading Bioactivity FGFR2-BICC1 Fusion is present in 0.10% of AACR GENIE cases, with intrahepatic cholangiocarcinoma, adenocarcinoma of unknown primary, cholangiocarcinoma, adenocarcinoma of the gastroesophageal junction, and breast invasive ductal carcinoma having the greatest prevalence  FGFR2 Fusions in CCA. Hear from gastrointestinal oncologist Milind Javle, MD, as he discusses the role molecular profiling plays in identifying actionable genomic alterations in patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma, and explains why FGFR2 fusions and other rearrangements are of particular interest Derazantinib in Subjects With FGFR2 Gene Fusion-, Mutation- or Amplification- Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma (FIDES-01) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government FGFR2 fusions with several fusion partners have been discovered in approximately 15% of intrahepatic cholangiocarcinoma cases 21,24. Some FGFR1 gene fusions have been observed in patients with.
This abnormality is a fusion between part of the FGFR2 gene to part of one of several other genes. The result is a cancer protein that constantly activates oncogenic FGFR2 signaling. The clinical utility of therapeutically targeting these tumor alterations are topics of current clinical trial investigations This is an important milestone for patients diagnosed with FGFR2-fusion-driven cholangiocarcinoma who have recurred after first-line therapy and are in need of targeted options for further treatment, said Susan Moran, M.D., M.S.C.E., Chief Medical Officer for QED KLK2-FGFR2 fusion was identified in a prostate cancer patient and was sensitive to FGFR inhibition by infigratinib. A. Expression of FGFR2 in a patient harboring the KLK2-FGFR2 gene fusion. A pileup of all reads is shown with the black vertical line representing the fusion breakpoint (FGFR2: blue; KLK2: orange)
The FDA Friday approved pemigatinib for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or. PEMAZYRE (pemigatinib) is the first FDA-approved treatment for adult patients with previously treated, unresectable locally advanced or metastatic CCA with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test. 1 This indication is approved under accelerated approval based on overall response rate and duration of response The U.S. Food and Drug Administration (FDA) approved Truseltiq (infigratinib) for patients with previously-treated locally advanced or metastatic cholangiocarcinoma (CCA) with an FGFR2 fusion or rearrangement. The announcement was made by BridgeBio Pharma through its affiliate QED Therapeutics and Helsinn Group. BridgeBio and Helsinn Group's affiliate, Helsinn Therapeutics, will jointly. FGFR2-BICC1: A Subtype Of FGFR2 Oncogenic Fusion Variant In Cholangiocarcinoma And The Response To Sorafenib Xihui Ying,1 Jianfei Tu,1 Wenxian Wang,2 Xingliang Li,3 Chunwei Xu,4 Jiansong Ji1 1Department of Radiology, Lishui Central Hospital/Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Lishui, Zhejiang 323000, People's Republic of.
LARVOL VERI predictive biomarker evidence, FGFR2 fusion. Other names: FGFR2, BEK, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25, Fibroblast growth factor recepto Genetic alterations in the fibroblast growth factor receptor (FGFR) pathway are promising therapeutic targets in many cancers, including intrahepatic cholangiocarcinoma (ICC). The FGFR inhibitor BGJ398 displayed encouraging efficacy in patients with FGFR2 fusion-positive ICC in a phase II trial, but the durability of response was limited in some patients 265 Background: Treatment options for cholangiocarcinoma (CCA) after progression on first-line gemcitabine-based therapy are limited. Fibroblast growth factor receptor 2 (FGFR2) gene fusions occur in 13-17% of intrahepatic CCA. A single-arm, phase II study (NCT02150967) evaluated infigratinib, an ATP-competitive FGFR1-3-selective oral tyrosine kinase inhibitor, in previously-treated.
Last year, the FDA approved pemigatinib (Incyte's Pemazyre) as a treatment for FGFR2 fusion-positive, previously treated, unresectable, locally advanced, or metastatic cholangiocarcinoma and FoundationOne CDx as the test to identify eligible patients This multicentre, phase 1/2, open-label study enrolled adult patients with unresectable iCCA with FGFR2 fusion, who progressed, were intolerant or not eligible to first-line chemotherapy. Below is a list of common medications used to treat or reduce the symptoms of cholangiocarcinoma with fibroblast growth factor receptor 2 (fgfr2) fusion or other rearrangement Incyte (Nasdaq:INCY) today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Pemazyre ® (pemigatinib), a selective fibroblast growth factor receptor (FGFR) inhibitor, for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene 1 , worsening after cancer chemotherapy previously treated, unresectable locally advanced or metastatic CCA with an FGFR2 fusion or rearrangement.1 Pemigatinib is a small-molecule kinase inhibitor of FGFR1, 2 and 3 with IC 50 values of <2 nM.1 Constitutive FGFR signaling can support the proliferation and survival of malignant cells.
FGFR1 Fusion, FGFR2 Fusion, and FGFR3 Fusion are the most frequent biomarker inclusion criteria for pemigatinib clinical trials. Malignant solid tumor, cholangiocarcinoma, and urothelial carcinoma are the most common diseases being investigated in pemigatinib clinical trials [ 2 ] WILMINGTON, Del.--(BUSINESS WIRE)-- Incyte (Nasdaq:INCY) today announced that the European Commission (EC) has approved Pemazyre ® (pemigatinib) for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer with a FGFR2 fusion gene, worsening after cancer chemotherapy. In Europe, Pemazyre is approved. Learn about a targeted treatment for cholangiocarcinoma that is FDA-approved. Prescribing Information with clinical results and Important Safety Information
As FGFR fusion can trigger the upregulation of FGFR expression, we determined the expression levels of FGFR2 in fusion-positive cases. Expression of FGFR2 was significantly higher in tumors with FGFR2 fusion compared with tumors without FGFR2 fusion (P < .0001; Fig 3C). This result confirmed that FGFR2 upregulation is a tumor-specific event FGFR2 fusion kinase is a promising candidate for tar-geted therapy in CC. Materials and Methods Clinical Samples. Clinical specimens of cholangio-carcinoma, gastric cancer, hepatocellular carcinoma, and colorectal cancer were provided by the National Cancer Center Biobank, Japan. Total RNA wa Intrahepatic cholangiocarcinoma is an aggressive cancer of the bile duct with few treatment options and a below 10% five-year survival rate. Here Sia et al. show a novel FGFR2-PPHLN1 fusion and. Thus, the PPHLN1 moiety drives dimerization of the FGFR2-PPHLN1 fusion protein, potentially leading to ligand-independent hyperactivation of FGFR2 kinase domain. Several pan-FGFR tyrosine kinase inhibitors (TKIs) have been studied clinically for treating FGFR2-fusion specific ICC patients, including BGJ398, Ponatinib, and PD173074
Documented FGFR2 gene fusion, mutation, or amplification per local testing of blood and/or tumor Additional FGFR2 alterations/tumor types may be considered for the Part 1 dose escalation Part 2 dose expansion patients must additionally meet the group requirements detailed below with FGFR2 fusion-positive ICC treated with BGJ398; this study revealed the emergence of the FGFR2 V565F gatekeeper mutation at progression in all 3 patients, 2 of whom also had additional FGFR2 kinase domain mutations (17). Rapid autopsy in one patient revealed three different FGFR2 kinas (FGFR2) fusion or rearrangement and would be commercialized under the brand name Pemazyre. Cholangiocarcinoma is a rare cancer that forms in the bile duct. It is classied based on its origin: intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver Conclusions: Infigratinib is associated with promising anticancer activity and a manageable AE profile in patients with advanced, refractory CCA with an FGFR2 gene fusion or rearrangement. A phase III study of infigratinib versus gemcitabine/cisplatin is ongoing in the front-line setting (NCT03773302) The FGFR2 : FAM76A fusion gene is one of the highly promising ovarian cancer biomarkers detectable in ctNAs. Herein, we introduce a new amplification-free electrochemical assay for the detection of FGFR2 : FAM76A fusion gene in ctNAs extracted from ovarian cancer patients
Chromosomal translocations involving fibroblast growth factor receptor 2 (FGFR2) gene at the breakpoints are common genetic lesions in intrahepatic cholangiocarcinoma (ICC) and the resultant fusion protein products have emerged as promising druggable targets.However, predicting the sensitivity of FGFR2 fusions to FGFR kinase inhibitors is crucial to the prognosis of the ICC-targeted therapy PubMed: BICC1 [Title/Abstract] AND FGFR2 [Title/Abstract] AND fusion [Title/Abstract] Functional or gene categories assigned by FusionGDB annotation. Oncogene involved fusion gene, in-frame and retained their domain. Kinase involved fusion gene, inframe and retained kinase domain. * DoF score (Degree of Frequency) = # partners X # break points. Fusion gene information: Fusion gene name: CCAR2_FGFR2: Fusion gene ID: 5752: Hgene: Tgene: Gene symbol: CCAR2. FGFR2. Gene ID: 57805. 2263. Gene name: cell cycle and. Considering taking medication to treat cholangiocarcinoma with fibroblast growth factor receptor 2 (fgfr2) fusion or other rearrangement? Below is a list of common medications used to treat or. This is an important milestone for patients diagnosed with FGFR2-fusion-driven cholangiocarcinoma who have recurred after first-line therapy and are in need of targeted options for further treatment, Dr. Susan Moran, chief medical officer of QED Therapeutics, said in a press release from the company
FGFR2 fusion indicates a fusion of the FGFR2 gene, but the fusion partner is unknown. G183fs frameshift: loss of function - predicted: FGFR2 G183fs results in a change in the amino acid sequence of the Fgfr2 protein beginning at aa 183 of 821, likely resulting in premature truncation of the functional protein (UniProt.org) The most common FGFR2 fusion partner was BICC1, which was observed in 25% (n = 27) of patients, followed by AHCYL1, which was noted in 3.7% (n = 4) of patients. Interestingly, 35% of patients had novel fusion partners, noted Javle. The median age of study participants was relatively low, according to Javle, at 53 years RNA sequencing targeting 1385 genes including FGFR2 was performed on the 25 patients determined to be FGFR2-FISH positive, and in-frame FGFR2 fusion transcripts were detected in 19 cases (Table 2). Fourteen kinds of FGFR2 fusion partner genes were identified, and FGFR2-BICC1 was frequently detected (4/19)
Patients without central confirmation of an FGFR2 fusion by the central FISH test will be assessed on a case-by-case basis. Negative FISH or NGS test: tissue may be submitted to the central laboratory designated by the Sponsor, and patients may only be enrolled if the central test is positive FGFR2-ACSL5 fusion transcript identified by RNA sequencing. The numbers of supporting reads of wild-type and fusion transcripts obtained are indicated below the respective diagrams. The number of supporting reads for the fusion junction suggested that the fusion form was dominantly expressed in the post-progression cancer
The gene view histogram is a graphical view of mutations across FGFR2. These mutations are displayed at the amino acid level across the full length of the gene by default. Restrict the view to a region of the gene by dragging across the histogram to highlight the region of interest, or by using the sliders in the filters panel to the left FOENIX-CCA2 (NCT02052778) is an ongoing global, open-label phase 2 study of patients with unresectable locally advanced or metastatic iCCA harboring an FGFR2 fusion or rearrangement. A total of. A fusion of the prohibitin-containing protein ER lipid raft associated 2 (ERLIN2) with FGFR1 has been described in breast cancer, and a solute carrier family 45 member 3 (SLC45A3)-FGFR2 gene. FGFR CDx Molecular Analysis is a qualitative RT-PCR assay, FDA-approved for detection of four point mutations in the FGFR3 gene (p.R248C, p.S249C, p.G370C and p.Y373C) and two FGFR3 fusions (FGFR3:TACC3v1 and FGFR3:TACC3v3) to identify certain urothelial carcinoma patients for treatment with BALVERSA™ (erdafitinib)