Journal: Signal Transduction and Targeted Therapy
Article Title: Oncogenic gene fusions in cancer: from biology to therapy
doi: 10.1038/s41392-025-02161-7
Figure Lengend Snippet: History and milestones of oncogenic fusion detection. 1956 . Karyotyping discovered. 1960 . Philadelphia chromosome discovery and characterization ( 1973 ). 1977 . Sanger sequencing. , 1980 . Discovery of CTNNB1 - PLAG1 . , , 1982 . Oncogenes isolated. FISH. 1985 . RET fusion. 1986 . ROS1 fusion; NTRK fusion. 1992 . EWS-FLI fusion. 1995 . BCR-ABL sequenced. 1998 . ETV6 - NTRK3 fusion; companion diagnostics. 2001 . Imatinib approval. 2003 . PDGFR fusions. 2004 . Mitelman database analysis. 2005 . TMPRSS2-ETS fusion; BRAF fusion; NGS sequencing. 2006 . TCGA; imatinib and dasatinib approval. , 2007 . EML4-ALK fusion; 358 fusions reported in Mitelman database; nilotinib approval. 2008 . NGS in cancer cells. , 2011 . Sequencing of 7 patients with prostate cancer (Illumina GA II); VTI1A-TCF7L2 in CRC (Illumina GA II); MI-Oncoseq; crizotinib accelerated approval plus CDx. 2012 . Bosutinib and ponatinib approval. , 2013 . NTRK1 fusions; FGFR fusions; NRG1 fusions; CD74-NRG1; first FDA authorization for next-generation sequencer. 2014 . FGFR2 fusion; computational fusion detection tools; TCGA analysis; ceritinib approval. 2015 . RET and ROS1 fusions; HER2 ; alectinib approval. 2016 . EGFR fusions; BRAF fusion study; crizotinib approval. 2017 . Testing panel approvals; , , – OncoKB. 2018 . TCGA cohort analysis; larotrectinib approval. 2019 . Entrectinib approval. 2020 . TCGA/CCLE analysis; Archer Dx; liquid biopsy approvals; , FoundationOne CDx approval; pemigatinib, brigatinib, pralsetinib, and selpercatinib approvals. , , , 2022 . Functional genomics approach to fusion characterization; futibatinib approval. 2023 . FoundationOne Liquid CDx; repotrectinib approval in NSCLC. 2024 . Repotrectinib; zenocutuzumab; and tovorafenib approval. ALL acute lymphoblastic leukemia, BCR-ABL1 breakpoint cluster region-Abelson 1, BRAF B-Raf proto-oncogene. CCA cholangiocarcinoma, CCLE Cancer Cell Line Encyclopedia, CD74 cluster of differentiation 74, CDx companion diagnostic, CEL chronic eosinophilic leukemia, CML chronic myelogenous leukemia, CRC colorectal cancer, CTNNB1-PLAG1 beta-catenin-pleomorphic adenoma gene 1, DFSP dermatofibrosarcoma protuberans, EGFR epidermal growth factor receptor, EML4-ALK echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, ESMO European Society of Medical Oncology, ETV6-NTRK3 ETS variant transcription factor 6-neurotrophic tyrosine receptor kinase 3, EWS-FLI ewing sarcoma breakpoint region 1-Friend leukemia integration 1 transcription factor, FDA US Food and Drug Administration, FGFR fibroblast growth factor receptor, FISH fluorescence in situ hybridization, HER2 human epidermal growth factor receptor 2, HES hypereosinophilic syndrome, MDS myelodysplastic syndromes, MPN myeloproliferative neoplasms, MSK Memorial Sloan Kettering, NGS next generation sequencing, NRG1 neuregulin-1, NSCLC non-small cell lung cancer, NTRK neurotrophic tyrosine receptor kinase, PDGFR platelet-derived growth factor receptor, refr. refractory, RET rearranged during transfection, ROS1 ROS proto-oncogene 1, TCGA The Cancer Genome Atlas Program, TMPRSS2-ETS transmembrane serine protease 2-erythroblast transformation specific, VTI1A-TCF7L2 vesicle transport through interaction with T-SNAREs 1A-transcription factor 7 like 2
Article Snippet: , NCT04093362 (FOENIX-CCA3) , Futibatinib (kinase inhibitor) , Advanced, metastatic, or recurrent unresectable iCCA , FGFR2 fusions/ rearrangements , Taiho Oncology, Inc .
Techniques: Sequencing, Isolation, Functional Assay, Diagnostic Assay, Variant Assay, Fluorescence, In Situ Hybridization, Next-Generation Sequencing, Derivative Assay, Transfection, Transformation Assay