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BIOMARKER:

FGFR2 mutation

i
Other names: FGFR2, BEK, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25, Fibroblast growth factor receptor 2
Entrez ID:
3d
Molecular pathology of gastrointestinal neoplasms (PubMed, Magy Onkol)
The responsiveness of gastrointestinal stromal tumors to imatinib requires validation via molecular testing. Patients diagnosed with pancreatic cancer may see enhanced survival rates by targeted therapy addressing microsatellite instability and BRCA mutations. In bile duct malignancies, especially intrahepatic cholangiocarcinoma of the small duct variant, the analysis of IDH1 mutations and FGFR2 fusions presents new treatment prospects.
Review • Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CLDN18 (Claudin 18) • BRCA (Breast cancer early onset)
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KRAS mutation • BRAF mutation • HER-2 amplification • NRAS mutation • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • BRCA mutation • IDH1 mutation + FGFR2 fusion
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imatinib
5d
Genomic correlates of response and resistance to the irreversible FGFR1-4 inhibitor futibatinib based on biopsy and circulating tumor DNA profiling. (PubMed, Ann Oncol)
In this largest and most systematic analysis of acquired resistance to an FGFR inhibitor from prospective clinical trials, emergence of secondary FGFR2 kinase domain mutations was observed in most patients receiving clinical benefit to futibatinib. ctDNA analysis shows clinically relevant potential as a noninvasive method for assessing genomic profiles, identifying patients who may benefit from FGFR inhibitor treatment, and exploring acquired resistance mechanisms.
Journal • Circulating tumor DNA • Biopsy
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TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR2 amplification • FGFR1 rearrangement • FGFR3 amplification • FGFR2 N550K
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Lytgobi (futibatinib)
11d
Molecular testing of gastrointestinal tumours - current status and future prospects. (PubMed, Rozhl Chir)
In gallbladder and biliary tract cancers, we are mainly looking for IDH1 and IDH2 mutations, FGFR2 gene fusions and mutations, HER2 amplifications or mutations, as well as mutations of BRAF or BRCA1/2. All results should be discussed within the molecular tumor board.
Review • Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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PD-L1 expression • BRCA2 mutation • BRCA1 mutation • BRAF mutation • HER-2 amplification • NRAS mutation • HER-2 expression • IDH2 mutation • FGFR2 mutation • FGFR2 fusion • HER-2 amplification + PD-L1 expression
21d
Use of 3' Rapid Amplification of cDNA Ends (3' RACE)-Based Targeted RNA Sequencing for Profiling of Druggable Genetic Alterations in Urothelial Carcinomas. (PubMed, Int J Mol Sci)
Overall, more than half of the UCs had potentially druggable genetic alterations. The proposed NGS panel permits comprehensive and cost-efficient analysis of UC-specific molecular targets and may be considered in clinical routine.
Journal • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1)
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PD-L1 expression • HER-2 overexpression • BRAF mutation • PIK3CA mutation • HER-2 expression • FGFR2 mutation • FGFR2 fusion • FGFR2 amplification • RAS mutation • PIK3CA overexpression
24d
Expert Consensus on the Diagnosis and Treatment of FGFR Gene-Altered Solid Tumors. (PubMed, Glob Med Genet)
For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.
Review • Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR2 mutation • FGFR2 fusion • FGFR3 mutation
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Balversa (erdafitinib) • Pemazyre (pemigatinib)
1m
Tissue-based Next Generation Sequencing (NGS) for Patients with Advanced Solid Tumors: the experience of Verona University Hospital (AIOM 2024)
Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.
Clinical • Next-generation sequencing • BRCA Biomarker • Metastases
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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BRAF V600E • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • PTEN mutation • KIT mutation • FGFR2 mutation • RET mutation • MET mutation • KRAS G12 • ESR1 mutation • NTRK1 mutation • BRAF amplification
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FoundationOne® CDx • TruSight Oncology 500 Assay
1m
Advanced Intrahepatic Cholangiocarcinoma (iCCA): Investigating Co-Molecular Alterations (AIOM 2024)
The FGFR and IDH-1 pathways are the primary targets for therapy, with FGFR-2 and IDH-1 inhibitors, such as Pemigatinib and Ivosidenib respectively, already available on the market. This prospective study validates the prevalence of mutations documented in the literature and underscores the significance of NGS in presenting supplementary therapeutic avenues. Moreover, we demonstrated the role of other potential targets co-expressed with FGFR2 or IDH1 which could represent a crucial opportunity for novel combinations or sequences therapies.
BRCA Biomarker • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NTRK (Neurotrophic receptor tyrosine kinase) • CA 19-9 (Cancer antigen 19-9)
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TP53 mutation • KRAS mutation • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • CDKN2A mutation • BAP1 mutation • FGFR2 expression • FGFR2b expression
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FoundationOne® CDx
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Pemazyre (pemigatinib) • Tibsovo (ivosidenib)
1m
First results from the Italian cholangiocarcinoma dataset (ANITA): extended molecular profiling (EMP), access to targeted treatment (TT) and clinical characterization of FGFR2- rearranged and IDH1-mutated advanced biliary tract cancers (BTC) (AIOM 2024)
Among pts with EMP available, 64.2% had intrahepatic cholangiocarcinoma and 69.8% received CT1 (36.1% cisplatinum-gemcitabine). Despite a broader availability of EMP in advanced BTC in recent years, access to TT remains suboptimal even in referral Institutions. Our results demonstrate TT administration as a pivotal positive prognostic factor in a real-world setting, whilst FGFR2 or IDH1 alterations did not act as prognostic determinants per-se. Therefore, strategies aiming at improving the rate of patients receiving TT are warranted.
Clinical • Metastases
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FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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IDH1 mutation • FGFR2 mutation • FGFR2 fusion • IDH1 R132
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FoundationOne® CDx
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cisplatin • gemcitabine
1m
FGFR Inhibitors in Urothelial Cancer: From Scientific Rationale to Clinical Development. (PubMed, J Korean Med Sci)
Among these therapies, erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor for specific FGFR2 and FGFR3 alterations, is the only targeted therapy approved till now...Ongoing investigations exist on its use in non-muscle-invasive BC and in combination with drugs such as enfortumab vedotin in mUC...This review emphasizes the importance of FGFR inhibition in UC and the optimization of its use in clinical practice. Moreover, it underscores the ongoing efforts to evaluate combination strategies and early treatment testing to enhance the effectiveness of targeted therapies for UC.
Review • Journal • IO biomarker
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TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • RB1 (RB Transcriptional Corepressor 1)
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TP53 mutation • FGFR2 mutation • FGFR3 mutation
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Balversa (erdafitinib) • Padcev (enfortumab vedotin-ejfv)
1m
Redefining pancreatic cancer management with tumor-agnostic precision medicine. (PubMed, Carcinogenesis)
Despite the rarity of NTRK fusions in pancreatic cancer, larotrectinib and entrectinib have exhibited effectiveness in NTRK fusion-positive pancreatic cancers. Additionally, repotrectinib, a next-generation NTRK inhibitor, has shown promising activity in NTRK positive pancreatic cancer patients who have developed acquired resistance to previous NTRK inhibitors. Immune checkpoint inhibitors, such as pembrolizumab and dostarlimab, have proven to be effective in dMMR/MSI-H pancreatic cancers...It is crucial to continue implementing comprehensive screening strategies that encompass the ability to detect all these tumor-agnostic biomarkers. This will be essential in identifying pancreatic cancer patients who may benefit from these therapies.
Journal • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Pan tumor
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • KRAS G12C • HER-2 overexpression • BRAF mutation • BRAF V600 • RET fusion • FGFR2 mutation • FGFR2 fusion • ALK fusion • NRG1 fusion • KRAS G12 • NTRK positive • NTRK fusion
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Keytruda (pembrolizumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Jemperli (dostarlimab-gxly) • Augtyro (repotrectinib)
1m
Genetic, Epigenetic, and Microenvironmental Drivers of Cholangiocarcinoma. (PubMed, Am J Pathol)
This review explores the multifaceted genetic, epigenetic and microenvironmental drivers of CCA. Understanding these diverse mechanisms is essential for characterizing the complex pathways of CCA carcinogenesis and developing targeted therapies to improve patient outcomes.
Review • Journal
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FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)
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IDH1 mutation • ARID1A mutation • FGFR2 mutation • BAP1 mutation
2ms
Ductal pancreatic cancer interception by FGFR2 abrogation. (PubMed, bioRxiv)
Mutant KRAS-expressing pancreatic intraepithelial neoplasias (PanINs), the precursor lesions of PDA, are prevalent in the average healthy adult but rarely advance to invasive carcinoma. Here, we discovered that FGFR2 promoted PDA progression by amplifying mutant KRAS signaling and that inactivation of FGFR2 intercepted disease progression.
Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • FGFR2 (Fibroblast growth factor receptor 2)
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KRAS mutation • FGFR2 mutation
2ms
Multigene Panel Next-Generation Sequencing Techniques in the Management of Patients with Metastatic Colorectal Carcinoma: The Way Forward for Personalized Treatment? A Single-Center Experience. (PubMed, Int J Mol Sci)
In total, 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited.
Journal • Next-generation sequencing • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • JAK1 (Janus Kinase 1)
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KRAS mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • FGFR2 mutation • KRAS G12 • ERBB3 mutation • MTOR mutation
2ms
Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer. (PubMed, J Hepatol)
Among patients with advanced BTC, ctDNA-based genotyping showed acceptable concordance with tissue genomic profiling. Liquid biopsy using ctDNA could be a valuable complement to tissue-based genomic analysis in BTC.
Journal • BRCA Biomarker • Circulating tumor DNA • Metastases • Discordant
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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BRCA2 mutation • BRCA1 mutation • HER-2 amplification • PIK3CA mutation • IDH1 mutation • MET amplification • FGFR2 mutation • FGFR2 fusion • MET mutation • PIK3CA amplification
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AlphaLiquid® 100
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cisplatin • gemcitabine
2ms
Clinical utility of liquid-based comprehensive genomic profiling (CGP) in gastrointestinal stromal tumors (GIST) (DGHO 2024)
55% (42/77) of liquid samples with a KIT -driver mutation had a co-occurring imatinib-resistant alteration, and a minority of cases harbored non- KIT mechanisms of resistance such as FGFR2 fusion, BRAF or EGFR alterations... Known driver and TKI-resistant mutations are identified in liquid biopsies of patients with GIST, with high concordance to tissue in the presence of elevated TF. Liquid biopsy may be valuable in the molecular classification of GIST during the medical management of advanced disease.
Clinical • Stroma
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1)
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KIT mutation • FGFR2 mutation • FGFR2 fusion • NF1 mutation • KIT exon 13 mutation • KIT exon 17 mutation
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FoundationOne® CDx • FoundationOne® Liquid CDx
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imatinib
2ms
Genomic and transcriptomic profiling of pre- and postneoadjuvant chemotherapy triple negative breast cancer tumors. (PubMed, Cancer Sci)
To advance our understanding of the role of breast cancer driver genes' mutational status with pathological complete response (pCR; ypT0/isypN0) prediction and to identify distinct gene sets for MTIs like eribulin and paclitaxel, we carried out targeted genomic (n = 50) and whole transcriptomic profiling (n = 64) of TNBC tumor samples from the Japan Breast Cancer Research Group 22 (JBCRG-22) clinical trial. Differential enrichment analysis of the HRD-high group posttreatment tumors revealed significant correlation (p = 0.006) of the glycan degradation pathway. FGFR2 expression and the differentially enriched pathways play a role in the response and resistance to MTIs containing carboplatin treatment in TNBC patients.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • HRAS (Harvey rat sarcoma viral oncogene homolog) • BRCA (Breast cancer early onset)
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TP53 mutation • BRCA2 mutation • PIK3CA mutation • HRD • PTEN mutation • FGFR2 mutation • HRAS mutation • BRCA mutation • FGFR2 expression • FGFR2b expression • High HRD score
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carboplatin • paclitaxel • Halaven (eribulin mesylate)
2ms
Evolving therapeutic landscape of advanced biliary tract cancer: from chemotherapy to molecular targets. (PubMed, ESMO Open)
In addition to the most common alterations such as isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations, fibroblast growth factor receptor 2 (FGFR2) fusions, and alterations, we will also discuss less frequently encountered alterations such as BRAF V600E mutation and neurotrophic tyrosine kinase receptor gene (NTRK) fusion. We highlight the importance of molecular profiling in guiding therapeutic decisions and emphasize the need for continued research to optimize and expand targeted treatment strategies for this aggressive malignancy.
Review • Journal • IO biomarker • Metastases
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BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • BRAF V600 • FGFR2 mutation • FGFR2 fusion • IDH mutation + BRAF V600E
3ms
Identification of potent biparatopic antibodies targeting FGFR2 fusion driven cholangiocarcinoma. (PubMed, bioRxiv)
Thus, biparatopic antibodies may serve as new treatment options for patients with FGFR2-altered cholangiocarcinoma. We identify biparatopic FGFR2 antibodies that are effective against FGFR2 fusion driven cholangiocarcinoma.
Journal
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FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 mutation • FGFR2 fusion
3ms
Genomic Landscape of Advanced Solid Tumors in Middle East and North Africa Using Circulating Tumor DNA (ctDNA) in Routine Clinical Practice. (PubMed, Oncology)
Overall, our findings provide insight into the genomic landscape of individuals with advanced solid organ malignancies from the MENA region and support the role of ctDNA in guiding therapeutic decisions.
Journal • BRCA Biomarker • Circulating tumor DNA • Metastases
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)
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BRAF V600E • EGFR mutation • PIK3CA mutation • BRAF V600 • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • ALK fusion
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Guardant360® CDx
3ms
Molecular profiling in biliary tract cancers: A national practice survey of French platforms (PubMed, Bull Cancer)
This national survey of French genetics platforms shows good performance and compliance with recommendations for molecular analysis. However, many medical, financial and organizational obstacles remain upstream of these platforms.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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TP53 mutation • BRAF mutation • HER-2 amplification • IDH1 mutation • FGFR2 mutation • FGFR2 fusion
3ms
REFOCUS: a First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients with ICC and Other Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=490, Active, not recruiting, Relay Therapeutics, Inc. | Trial completion date: Oct 2024 --> Aug 2025 | Trial primary completion date: Jun 2024 --> Sep 2024
Trial completion date • Trial primary completion date • Metastases
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FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 mutation • FGFR2 fusion • FGFR2 amplification
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lirafugratinib (RLY-4008)
3ms
Distinct phenotypic consequences of cholangiocarcinoma-associated FGFR2 alterations depend on biliary epithelial maturity. (PubMed, bioRxiv)
Importantly, we found that both the trafficking and signaling of normal FGFR2 and the phenotypic consequences of FGFR2 mutants are influenced by the epithelial state of the cell. Unexpectedly, we found that different tumor-driving FGFR2 mutants disrupt biliary morphogenesis in completely different and clinically relevant ways, informing our understanding of morphogenesis and tumorigenesis and highlighting the importance of convergent studies of both.
Journal
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FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 mutation
3ms
Targeting mTOR signaling for the treatment of intrahepatic cholangiocarcinoma with TSC1/ARID1A mutations: a case report with an unexpected response. (PubMed, Ther Adv Med Oncol)
These results suggest the existence of an mTOR oncogenic addiction in biliary tract cancer. Our results support the interest in performing exome sequencing in liver cancers and the potential to identify actionable mutations with important therapeutic issues.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ARID1A (AT-rich interaction domain 1A) • TSC1 (TSC complex subunit 1)
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IDH1 mutation • ARID1A mutation • FGFR2 mutation • FGFR2 fusion • TSC1 mutation
3ms
Early Optical Coherence Tomography Signs of Erdafitinib-Induced Retinopathy. (PubMed, Cureus)
The drug may exert toxic effects on retinal pigment epithelium, which may be seen through interval OCTs and visualization of the interdigitation zone. Therefore, pronunciation of the ellipsoid and interdigitation zone on OCT may allow for surveillance of early manifestations of erdafitinib-induced retinal toxicity.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3)
|
FGFR2 mutation • FGFR3 mutation
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Balversa (erdafitinib)
3ms
Emerging Tumor-Agnostic Molecular Targets. (PubMed, Mol Cancer Ther)
Emerging biomarkers with the potential for clinical actionability across tumor types include gene fusions involving NRG1, FGFR1/2/3, BRAF, and ALK, mutations in TP53 Y220C, KRAS G12C, FGFR2/3, and BRAF non-V600 (Class II). We explore the growing evidence for clinical actionability of these biomarkers in patients with advanced solid tumors.
Journal • Pan tumor
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • NRG1 (Neuregulin 1)
|
TP53 mutation • KRAS mutation • KRAS G12C • BRAF mutation • FGFR2 mutation • FGFR2 fusion • ALK fusion • ALK mutation • NRG1 fusion • KRAS G12 • FGFR1 fusion • TP53 Y220C
3ms
Discovery of TYRA-300: First Oral Selective FGFR3 Inhibitor for the Treatment of Urothelial Cancers and Achondroplasia. (PubMed, J Med Chem)
The pan-FGFR inhibitor erdafitinib was approved for the treatment of mUC with FGFR3 alterations but is limited due to FGFR isoform off-target toxicities and the development of on-target gatekeeper resistance mutations. TYRA-300 (22) was conceived using a structure-based approach as a potent FGFR3-selective inhibitor to avoid the toxicities associated with inhibition of FGFR1, FGFR2, and FGFR4, and to be agnostic for the FGFR3 gatekeeper mutations. TYRA-300 is being evaluated in a Phase 1 clinical trial in urothelial cancers and solid tumors, with intention to initiate Phase 2 studies in urothelial cancers and achondroplasia.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR4 (Fibroblast growth factor receptor 4)
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FGFR2 mutation • FGFR3 mutation • FGFR mutation • FGFR3 G380R
|
Balversa (erdafitinib) • TYRA-300
3ms
Analytic validation of an FGFR -focused cell-free DNA liquid biopsy assay (FGFR-Dx). (PubMed, medRxiv)
Custom FGFR synthetic reference standards representing both single nucleotide variants (SNVs) and gene rearrangements were utilized at a range of variant frequencies and revealed a detection limit of 0.5% with sensitivities of 97.2% and 92.9% for SNVs and rearrangements, respectively. Furthermore, FGFR-Dx detected rearrangements and identified the intronic breakpoints from cfDNA collected from 13 of 15 patients with known FGFR fusions.
Journal • Liquid biopsy • Biopsy
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor)
|
FGFR2 mutation • FGFR3 mutation • FGFR fusion • FGFR2 rearrangement
3ms
Racial and Sex Differences in Genomic Profiling of Intrahepatic Cholangiocarcinoma. (PubMed, Ann Surg Oncol)
Distinct genomic variations exist in iCCA across race and sex. Differences in mutational profiles of iCCA patients highlight the importance of including a diverse patient population in iCCA clinical trials as well as the importance of recognizing different genetic drivers that may be targetable to treat distinct patient cohorts.
Journal
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TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BAP1 (BRCA1 Associated Protein 1)
|
TP53 mutation • IDH1 mutation • FGFR2 mutation • BAP1 mutation
4ms
Understanding and Overcoming Resistance to Selective FGFR inhibitors Across FGFR2-Driven Malignancies. (PubMed, Clin Cancer Res)
At progression to FGFR inhibitors, FGFR2-driven malignancies are characterized by high intra- and inter-patient molecular heterogeneity, particularly in cholangiocarcinoma. Resistance to FGFR inhibitors can be overcome by sequential, molecularly-oriented treatment strategies across FGFR2-driven tumors.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • TSC1 (TSC complex subunit 1) • BICC1 (BicC Family RNA Binding Protein 1)
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PIK3CA mutation • FGFR2 mutation • TSC1 mutation
|
everolimus • Balversa (erdafitinib) • Lytgobi (futibatinib) • Pemazyre (pemigatinib) • lirafugratinib (RLY-4008)
4ms
The Importance of Sub-Typing: A Rare Case of Asymptomatic Intestinal Type Periampullary Carcinoma (ACG 2024)
Further research and awareness is necessary to highlight the different types of ampullary cancer given the significant clinical implications. Figure: Image 1: (A) Endoscopic imaging of ampullary mass (B) EUS depicting ampullary mass
Clinical
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • CDX2 (Caudal Type Homeobox 2)
|
TP53 mutation • EGFR mutation • BRAF mutation • FGFR2 mutation • FGFR2 amplification • BRAF amplification
|
Guardant360® CDx
|
5-fluorouracil
5ms
Transformative diagnostics in urothelial carcinoma: Utilizing targeted NGS and LP-WGS for non-invasive detection and personalized medicine (ESMO 2024)
The utDNA and uCNB analyses in this study demonstrated high sensitivity and specificity, offering promising non-invasive diagnostic options for UC. These methods also have the potential to facilitate personalized therapy, improving patient management in urothelial carcinoma.
Next-generation sequencing
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TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2)
|
TP53 mutation • FGFR2 mutation
|
PredicineCARE™
6ms
Detection of FGFR3 mutations and fusions in bladder cancer samples: Comparison of the MODAPLEX FGFR panel with therascreen FGFR Kit (ECP 2024)
The MODAPLEX FGFR panel allows the stratification of bladder cancer patients by determination of the FGFR3 mutational and FGFR2/3 fusion status. The PCR-based FGFR assessment by MODAPLEX FGFR panel and therascreen FGFR kit is highly concordant (78/79). The MODAPLEX assays enable fast, local FGFR assessment in a multiplexed one-step approach within few hours.
FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)
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FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR3 S249C • FGFR3 Y373C • FGFR3 fusion • FGFR3 G370C • FGFR3 R248C • FGFR3 K650E
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Uromonitor®
6ms
FGFR alterations in a contemporary real-world cohort of advanced or metastatic urothelial carcinoma (ECP 2024)
Based on reflex molecular analysis performed on consecutive advanced/metastatic BCs, we found FGFR alterations to be present in approximately 17% of UCs, with FGFR3 being more frequently altered than FGFR1 and FGFR2 genes. These patients could gain clinical benefits from receiving a FGFR inhibitor such as erdafitinib which is an approved drug to treat FGFR-altered BCs lacking response to chemotherapy. Future studies will include a larger cohort to assess the correlation of FGFR alterations with histologic subtypes of invasive UC.
Real-world evidence • Clinical • Real-world • Metastases
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR mutation • FGFR3 fusion
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Oncomine™ Comprehensive Assay v3M • Oncomine™ Comprehensive Assay Plus
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Balversa (erdafitinib)
7ms
Genetic/Epigenetic Alteration and Tumor Immune Microenvironment in Intrahepatic Cholangiocarcinoma: Transforming the Immune Microenvironment with Molecular-Targeted Agents. (PubMed, Liver Cancer)
So far, standard systemic therapy for advanced iCCA has been a combination of gemcitabine and cisplatin. Combination approaches that target both the tumor and immune system hold promise for improving the outcomes of patients with iCCA. Further research and clinical trials are needed to validate these approaches and optimize the treatment strategies for iCCA.
Review • Journal • IO biomarker
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FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • IFNG (Interferon, gamma) • SOCS1 (Suppressor Of Cytokine Signaling 1)
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FGFR2 mutation
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cisplatin • gemcitabine
7ms
Combined analysis of albumin in situ hybridisation and C reactive protein immunohistochemistry for the diagnosis of intrahepatic cholangiocarcinoma: towards a molecular classification paradigm. (PubMed, J Clin Pathol)
In conclusion, we propose a sequential diagnostic approach for iCCA, integrating CRP immunohistochemistry and Alb-ISH. This may improve the accuracy of CCA classification and pave the way towards a molecular-guided CCA classification.
Journal
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KRAS (KRAS proto-oncogene GTPase) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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KRAS mutation • IDH2 mutation • FGFR2 mutation
7ms
Intrahepatic cholangiocarcinoma with FGFR alterations: A series of Chinese cases with an emphasis on their clinicopathologic and genetic features. (PubMed, Dig Liver Dis)
Our study further revealed the clinicopathological and genetic features of FGFR-altered iCCA and demonstrated that its occurrence may show regional or ethnic variability and is less common in the Chinese population. A significant number of LD-type iCCA cases also have FGFR alterations rather than the SD type.
Journal • Tumor mutational burden
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TMB (Tumor Mutational Burden) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR2 mutation • TMB-L • FGFR2 rearrangement
7ms
Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma. (PubMed, Cancers (Basel))
Other options for targeted treatment include EGFR- or VEGF-dependent pathways, which are known to be overexpressed or dysregulated in this cancer type and are currently under clinical investigation. Targeted therapy in CCA is a hallmark of individualized medicine as these therapies aim to specifically block pathways that promote cancer cell growth and survival, leading to tumor shrinkage and improved patient outcomes based on the molecular profile of the tumor.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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HER-2 overexpression • BRAF mutation • FGFR2 mutation • FGFR2 fusion
8ms
XmAb20717 in Advanced Biliary Tract Cancers (clinicaltrials.gov)
P2, N=27, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial primary completion date: Mar 2024 --> Dec 2024
Trial primary completion date • Metastases
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FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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IDH1 mutation • FGFR2 mutation • FGFR2 fusion • NTRK fusion
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vudalimab (XmAb717)
8ms
Comprehensive Genomic Characterization in Ovarian Low-Grade and chemosensitive and chemoresistant High-Grade Serous Carcinomas. (PubMed, Oncology)
These results suggest that very low TMB and MYC, CCNE1 and AKT2 gains in SOC patients may be biomarkers related to platinum treatment efficacy. Thorough genomic characterization of SOCs prior to treatment might lead to more specific platinum-based chemotherapy therapy strategies.
Journal • Tumor mutational burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCNE1 (Cyclin E1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • YAP1 (Yes associated protein 1) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)
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FGFR2 mutation • TMB-L • FGFR3 fusion
8ms
Elucidating the Role of Wildtype and Variant FGFR2 Structural Dynamics in (Dys)Function and Disorder. (PubMed, Int J Mol Sci)
In this study, we utilize experimentally resolved structures of the FGFR2 tyrosine kinase domain and machine learning to capture the intrinsic structural dynamics, correlate it with functional regions and disease types, and enrich it with predicted structures of variants with currently no experimentally resolved structures. Our findings demonstrate the value of machine learning-enabled characterizations of structure dynamics in revealing the impact of mutations on (dys)function and disorder in FGFR2.
Journal
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FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 mutation
8ms
Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma. (PubMed, Cancers (Basel))
Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.
Review • Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)
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TP53 mutation • KRAS mutation • BRAF mutation • ARID1A mutation • FGFR2 mutation • FGFR2 fusion • BAP1 mutation
8ms
Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) in Cholangiocarcinoma (clinicaltrials.gov)
P2, N=55, Completed, TransThera Sciences (Nanjing), Inc. | Active, not recruiting --> Completed
Trial completion • Metastases
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR1 mutation • FGFR1 fusion • FGFR wild-type
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tinengotinib (TT-00420)