This report offers a thorough characterization of expected prevalence and expression levels for CSFs and NDFs with an NGS study of a broad scope. We describe ESR1 fusions in a cohort of thousands of breast tumors and show lower median expression levels relative to NDFs such as ALK, ROS1, and RET fusions. Our findings suggest that some CSFs, like ESR1 fusions in breast cancer, may be the result of tandem duplication with upstream partners, and may be subclonal and acquired later in cancer progression.

2 days ago

ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • CCDC170(Coiled-Coil Domain Containing 170) • RSPO3 (R-Spondin 3)

RET fusion • MET exon 14 mutation • ROS1 fusion • FGFR3 fusion • ER-CCDC170 fusion

Oncomine Precision Assay

Clinical Utility of Novel Fusion Detection by Amplicon-Based Next-Generation Sequencing versus Whole-Transcriptome Sequencing in Practice (AMP 2024)

In this real-world clinical dataset, WTS performed significantly worse than amplicon-based sequencing for detection of clinically meaningful fusions, predominantly due to a high QNS rate. It did not significantly increase the detection rate of novel fusions. Although amplicon-based methods may have limitations due to the inability to detect novel fusions, this can be overcome with design for additional targets, and is balanced by a superior ability to test a wide range of clinical samples without failure.

2 days ago

Clinical • Next-generation sequencing

ALK (Anaplastic lymphoma kinase) • FGFR3 (Fibroblast growth factor receptor 3) • NRG1 (Neuregulin 1) • KIF5B (Kinesin Family Member 5B) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CCDC6 (Coiled-Coil Domain Containing 6) • VTCN1 (V-Set Domain Containing T Cell Activation Inhibitor 1) • YAP1 (Yes associated protein 1) • STAT6 (Signal transducer and activator of transcription 6) • MAML2 (Mastermind Like Transcriptional Coactivator 2) • NAB2 (NGFI-A Binding Protein 2)

FGFR3 fusion

Oncomine™ Comprehensive Assay v3M

15d

TAS-120-203: Futibatinib and Pembrolizumab Combination in the Treatment of Advanced or Metastatic Urothelial Carcinoma (clinicaltrials.gov)

P2, N=43, Active, not recruiting, Taiho Oncology, Inc. | Trial primary completion date: Aug 2025 --> Mar 2024

15 days ago

Trial primary completion date • Metastases

FGFR3 mutation • FGFR1 mutation • FGFR1 fusion • FGFR3 fusion

Keytruda (pembrolizumab) • Lytgobi (futibatinib)

28d

Case report: a case of lung squamous cell carcinoma with a novel FGFR3-IER5L fusion mutation responding to anlotinib. (PubMed, Front Oncol)

Anlotinib is a small molecular multi-target tyrosine kinase inhibitor, which can inhibit the activity of kinases including vascular endothelial growth factor receptor 2/3 (VEGFR2/3), fibroblast growth factor receptor 1-4 (FGFR1-4), platelet-derived growth factor receptor α/β (PDGFRα/β), and c-Kit. The patient achieved partial response and the progression-free survival was 3.8 months.

28 days ago

Journal

KIT (KIT proto-oncogene, receptor tyrosine kinase) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • KDR (Kinase insert domain receptor)

FGFR3 fusion

Focus V (anlotinib)

30d

Rare Oncogenic Fusions in Pediatric Central Nervous System Tumors: A Case Series and Literature Review. (PubMed, Cancers (Basel))

Even within tumors harboring the same oncogenic fusions, a wide range of morphological, molecular and epigenetic entities can be observed. These findings highlight the need for caution when applying the fifth CNS WHO classification, as the vast majority of these fusions are not yet incorporated in the diagnosis, including grade evaluation and DNA methylation classification.

30 days ago

Review • Journal

ALK (Anaplastic lymphoma kinase) • FGFR3 (Fibroblast growth factor receptor 3) • BCOR (BCL6 Corepressor) • NTRK (Neurotrophic receptor tyrosine kinase)

ALK fusion • ROS1 fusion • FGFR3 fusion

FGFR3::TACC3 fusions in head and neck carcinomas: a study of nine cases highlighting phenotypic heterogeneity, frequent HPV association, and a morphologically distinct subset in favor of a putative entity. (PubMed, Virchows Arch)

A driver role of the FGFR3::TACC3 fusion in the first category (as a potential distinct entity) remains to be further studied. In the light of available FGFR-targeting therapies, delineation of these tumors and enhanced recognition is recommended.

1 month ago

Journal

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • AFF2 (AF4/FMR2 family member 2) • GATA3 (GATA binding protein 3)

FGFR3 fusion • AR expression

Genetic Profiling of Non-Small Cell Lung Cancer in Moroccan Patients by Targeted Next-Generation Sequencing. (PubMed, Technol Cancer Res Treat)

Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.

1 month ago

Journal • Retrospective data • PD(L)-1 Biomarker • IO biomarker • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PTEN mutation • RET mutation • ROS1 fusion • RET rearrangement • ERBB3 mutation • FGFR3 fusion • EGFR mutation + KRAS mutation

Oncomine Precision Assay

All-in-one bimodal DNA and RNA next-generation sequencing panel for integrative diagnosis of glioma. (PubMed, Pathol Res Pract)

Overall, our results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors.

1 month ago

Journal • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TERT (Telomerase Reverse Transcriptase)

EGFR mutation • NTRK2 fusion • FGFR3 fusion • TERT mutation • IDH mutation + NTRK fusion

2ms

Pluripotent stem cell-derived CTLs targeting FGFR3-TACC3 fusion gene in osteosarcoma. (PubMed, Int Immunopharmacol)

Findings were validated in in vivo experiments. This study suggests that iPSC-derived CTLs targeting FGFR3-TACC3 hold promise for personalized immunotherapy against osteosarcoma.

2 months ago

Journal • IO biomarker

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR3-TACC3 fusion • FGFR3 fusion • FGFR3 expression

4ms

Enhancing Clinical Utility: Oncomine Dx Target Test Augments Biomarker Detection in Advanced Non-Small-Cell Lung Cancer (IASLC-WCLC 2024)

Conclusions : The integration of ODxTT alongside single gene tests provides significant additional information without compromising the performance of single gene tests. With ODxTT's high success rate, this integration expands the scope of comprehensive therapeutic strategies for advanced lung cancer.

4 months ago

Clinical • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

BRAF V600E • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • RET fusion • EGFR exon 20 insertion • MET exon 14 mutation • ALK mutation • KRAS G12 • EGFR exon 20 mutation • ROS1 mutation • FGFR3 fusion

Oncomine™ Dx Target Test

4ms

Prevalence of gene rearrangement on ctDNA NGS and its targetability in patients with advanced breast cancer (ESMO 2024)

Initially, she received three cycles of Nabpaclitaxel and carboplatin and upon progression plasma ctDNA NGS was ordered and reported EML4-ALK fusion (0.7% VAF) in Nov 2022 resulting in treatment with alectinib. ctDNA CGP can provide genotyping at fast TAT for effective management of aBC. Fusions, though rare in aBC, should be considered for detection for targeted therapy.

4 months ago

Clinical • Tumor mutational burden • Next-generation sequencing • Circulating tumor DNA • Metastases

ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • TACC3 (Transforming acidic coiled-coil containing protein 3)

ALK positive • EML4-ALK fusion • ALK fusion • FGFR3 fusion

Guardant360® CDx

carboplatin • Alecensa (alectinib) • albumin-bound paclitaxel

4ms

Ultra-sensitive ctDNA NGS assay enhances genomic profiling for advanced HR-positive, HER2-negative breast cancer on endocrine therapy (ESMO 2024)

Plasma samples were collected after aromatase inhibitor treatment and before starting Fulvestrant... The ultra-sensitive ctDNA NGS assay outperformed standard liquid biopsy assays in detecting low-frequency mutations and those from samples with low tumor fractions in HR-positive, HER2-negative breast cancer. Its superior detection may help identify patients suitable for targeted therapies like PIK3CA and ESR1 inhibitors, improving early detection of treatment resistance and disease monitoring for more effective personalized treatment strategies.

4 months ago

BRCA Biomarker • Next-generation sequencing • Circulating tumor DNA • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • FGFR3 (Fibroblast growth factor receptor 3) • BAIAP2L1 (BAI1 associated protein 2 like 1) • BAIAP2 (BAR/IMD Domain Containing Adaptor Protein 2)

TP53 mutation • HR positive • HER-2 negative • PIK3CA mutation • FGFR3 fusion • FGFR3-BAIAP2L1 fusion • PTEN mutation + HR positive

PredicineCARE™

fulvestrant

5ms

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.

5 months ago

Real-world evidence • Clinical • Real-world • Metastases

FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor)

FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR mutation • FGFR3 fusion

Oncomine™ Comprehensive Assay v3M • Oncomine™ Comprehensive Assay Plus

Balversa (erdafitinib)

5ms

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.

5 months ago

FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR3 S249C • FGFR3 Y373C • FGFR3 fusion • FGFR3 G370C • FGFR3 R248C • FGFR3 K650E

Uromonitor®

6ms

Diffuse Gliomas with FGFR3::TACC3 Fusion: Morphological and Molecular Features and Classification Challenges. (PubMed, Cancers (Basel))

In conclusion, diffuse gliomas with FGFR3::TACC3 fusion do not constitute a distinct nosological entity, owing to their genetic and epigenetic diversity. Further studies are warranted to clarify the biological aggressiveness of tumors with low-grade histology to refine the grading and determine the optimal treatment strategy.

6 months ago

Review • Journal

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CD34 (CD34 molecule)

FGFR3 fusion

7ms

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.

7 months ago

Journal • Tumor mutational burden

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)

FGFR2 mutation • TMB-L • FGFR3 fusion

7ms

Patient with mediastinal carcinoma of unknown primary with RET fusion achieves durable response with RET inhibition. (PubMed, Anticancer Drugs)

The patient was initiated on selpercatinib, which was held after 3 weeks due to thrombocytopenia and hypertension. Pralsetinib was held during adjuvant chemoradiation for the GBM, and again for 4 weeks due to pneumonitis that resolved with steroids, and pralsetinib was restarted at a reduced dose. The patient has since demonstrated a stable reduction of the mediastinal mass for >15 months with RET inhibition therapy, despite several treatment interruptions.

7 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

TP53 (Tumor protein P53) • RET (Ret Proto-Oncogene) • FGFR3 (Fibroblast growth factor receptor 3) • TERT (Telomerase Reverse Transcriptase) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CCDC6 (Coiled-Coil Domain Containing 6)

TP53 mutation • RET fusion • FGFR3-TACC3 fusion • FGFR3 mutation • CCDC6-RET fusion • FGFR3 fusion • TERT mutation • TERT 124C>T

Retevmo (selpercatinib) • Gavreto (pralsetinib)

7ms

Genomic landscape of glioblastoma without IDH somatic mutation in 42 cases: a comprehensive analysis using RNA sequencing data. (PubMed, J Neurooncol)

RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.

7 months ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • SOX10 (SRY-Box 10)

TP53 mutation • EGFR mutation • FGFR3 fusion

7ms

TAS-120-203: Futibatinib and Pembrolizumab Combination in the Treatment of Advanced or Metastatic Urothelial Carcinoma (clinicaltrials.gov)

P2, N=46, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> May 2024

7 months ago

Enrollment closed • Trial primary completion date • Metastases

FGFR3 mutation • FGFR1 mutation • FGFR1 fusion • FGFR3 fusion

Keytruda (pembrolizumab) • Lytgobi (futibatinib)

7ms

FIDES-03: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma (clinicaltrials.gov)

P1/2, N=47, Terminated, Basilea Pharmaceutica | Phase classification: P1b/2 --> P1/2

7 months ago

Phase classification • Combination therapy

HER-2 (Human epidermal growth factor receptor 2) • FGFR2 (Fibroblast growth factor receptor 2)

HER-2 negative • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR fusion • FGFR1 fusion • FGFR3 fusion

Tecentriq (atezolizumab) • paclitaxel • Cyramza (ramucirumab) • derazantinib (ARQ 087)

8ms

FOENIX-CCA2: A Study of TAS-120 in Patients With Advanced Solid Tumors (clinicaltrials.gov)

P1/2, N=407, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed

8 months ago

Trial completion • Metastases

FGFR2 (Fibroblast growth factor receptor 2)

FGFR2 fusion • FGFR3 mutation • FGFR fusion • FGFR2 rearrangement • FGFR3 fusion

Lytgobi (futibatinib)

8ms

RT-PCR assay to detect FGFR3::TACC3 fusions in formalin-fixed, paraffin-embedded glioblastoma samples. (PubMed, Neurooncol Pract)

RT-PCR for FGFR3::TACC3 fusions can successfully be performed on FFPE material, with a specificity of 100% and (due to limited primer sets) a sensitivity of 83.3%. This assay allows for the identification of potential targeted treatment options when only formalin-fixed tissue is available.

8 months ago

Journal

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR3 overexpression • FGFR3 fusion • IDH wild-type • FGFR3 expression • FGF3 overexpression

8ms

SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)

P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

8 months ago

Trial completion date • Trial primary completion date

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)

HER-2 mutation • BAP1 mutation • AKT1 mutation • FGFR3 fusion • JAK3 mutation

9ms

The irreversible FGFR inhibitor KIN-3248 overcomes FGFR2 kinase domain mutations. (PubMed, Clin Cancer Res)

Thus, KIN-3248 is a novel FGFR1-4 inhibitor whose distinct activity profile against FGFR kinase domain mutations highlights its potential for the treatment of ICC and other FGFR-driven cancers.

9 months ago

Journal

FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3)

FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR3 fusion • FGFR3 V555M

KIN-3248

9ms

Real-World Clinical Performance of a DNA-Based Comprehensive Genomic Profiling Assay for Detecting Targetable Fusions in Nonsquamous NSCLC. (PubMed, Oncologist)

A well-designed DNA CGP assay is capable of robust fusion detection and these fusion calls are reliable for informing clinical decision-making. While DNA CGP detects most driver fusions, the clinical impact of fusion detection is substantial for individual patients and exhaustive efforts, inclusive of additional RNA-based testing, should be considered when an oncogenic driver is not clearly identified.

9 months ago

Real-world evidence • Journal • Real-world

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • FGFR2 fusion • ALK fusion • ROS1 fusion • FGFR3 fusion • ALK-ROS1 fusion

FoundationOne® CDx

9ms

RNASeq Analysis for Accurate Identification of Fusion Partners in Tumor Specific Translocations Detected by Standard FISH Probes in Hematologic Malignancies. (PubMed, Clin Pathol)

These are 3 cases in a series of several other concordant results, nevertheless, elucidate limitations when interpreting FISH results in clinical applications, particularly when other genes are included in probe design. In addition, when the observed FISH signals are atypical, this study illustrates the necessity to perform complementary laboratory assays, such as NGS and/or RNASeq, to accurately identify fusion genes in tumorigenic translocations.

9 months ago

Journal

FGFR3 (Fibroblast growth factor receptor 3) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor) • MEF2D (Myocyte Enhancer Factor 2D) • PVT1 (Pvt1 Oncogene) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)

FGFR3 fusion • MYC positive • FGFR3 positive • MEF2D-CSF1R fusion

9ms

Artificial Intelligence (AI) Assisted Detection of FGFR3 Alterations In Bladder Cancer From Scanned Whole Slide Images (WSI) of H&E Sections (USCAP 2024)

We developed an effective AI system for detecting phenotypes associated with FGFR3 abnormalities that may be targetable by FGFR inhibitors. This system may allow cost and time savings in comparison to existing assays to screen bladder carcinomas for additional diagnostic testing.

9 months ago

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR3-TACC3 fusion • FGFR3 mutation • FGFR3 S249C • FGFR3 Y373C • FGFR3 fusion • FGFR3 R248C

MSK-IMPACT

9ms

BGJ398 in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder (clinicaltrials.gov)

P=N/A, N=4, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

9 months ago

Trial completion date • Trial primary completion date

FGFR3 mutation • FGFR3 fusion

Truseltiq (infigratinib)

9ms

Genomic Landscape of NSCLC in the Republic of Ireland. (PubMed, JTO Clin Res Rep)

Actionable alterations were identified in 53.4% of the patients, and KRAS was the most common oncogenic driver alteration. Our study revealed a lower prevalence of patients whose tumor harbors ALK, ROS1, and RET fusions, compared with similar data sets.

9 months ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS G12C • BRAF mutation • HER-2 amplification • MET amplification • RET fusion • MET exon 14 mutation • ROS1 fusion • KRAS G12A • KRAS G12 • FGFR3 fusion • BRAF G469A • NTRK fusion

9ms

Differences in methylation profiles between long-term survivors and short-term survivors of IDH-wild-type glioblastoma. (PubMed, Neurooncol Adv)

A small group of patients with IDH-wild-type GBM survive more than 5 years. While there are few differences in the global methylation profiles of LTS compared to STS, our study highlights potential pathways involved in GBMs with a good or poor prognosis.

9 months ago

Journal

FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

FGFR3-TACC3 fusion • NF1 mutation • FGFR3 fusion • IDH wild-type

10ms

Identification of Piperazinyl-Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation. (PubMed, J Med Chem)

Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.

10 months ago

Journal

FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR4 (Fibroblast growth factor receptor 4)

FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR2 amplification • FGFR mutation • FGFR1 fusion • FGFR3 fusion • FGFR4 mutation

10ms

Atypical Histopathological Aspects of Common Types of Lung Cancer-Our Experience and Literature Review. (PubMed, Medicina (Kaunas))

Recent studies associated clear cell morphology with FGFR3-TACC3 fusion, suggesting that patients with this diagnosis may be potentially eligible for FGFR inhibitors. We described, for the first time, the pseudoangiosarcomatous pattern in a case of lung adenocarcinoma; to our knowledge this aspect has only been described until now in the context of squamous cell carcinomas.

10 months ago

Review • Journal

ALK (Anaplastic lymphoma kinase) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

ALK rearrangement • FGFR3-TACC3 fusion • FGFR3 fusion

10ms

Clinicopathological and Molecular Characteristics of IDH-Wildtype Glioblastoma with FGFR3::TACC3 Fusion. (PubMed, Biomedicines)

Our observations suggest that F3T3-positive GBM is a distinct molecular subgroup of the IDH-wildtype GBM. Both clinicians and pathologists should consider this rare entity in the differential diagnosis of diffuse astrocytic glioma to make an accurate diagnosis and to ensure appropriate therapeutic management.

10 months ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TERT (Telomerase Reverse Transcriptase) • TACC3 (Transforming acidic coiled-coil containing protein 3) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • EGFR mutation • EGFR amplification • PTEN mutation • MDM2 amplification • CDKN2A deletion • CDKN2A mutation • CDK4 amplification • FGFR3 fusion • TERT mutation • IDH wild-type • TERT promoter mutation • CDK4 mutation

10ms

TACC3: a multi-functional protein promoting cancer cell survival and aggressiveness. (PubMed, Cell Cycle)

A detailed understanding of the regulation of TACC3 expression, its key partners, and molecular functions in cancer cells is vital for uncovering the most vulnerable tumors and maximizing the therapeutic potential of targeting this highly oncogenic protein. In this review, we summarize the established and emerging interactors and spatiotemporal functions of TACC3 in cancer cells, discuss the potential of TACC3 as a biomarker in cancer, and therapeutic potential of its inhibition.

10 months ago

Review • Journal

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR fusion • FGFR3 fusion • TACC3 expression

10ms

NCCH2006/MK010 Trial (FORTUNE Trial) (clinicaltrials.gov)

P2, N=46, Active, not recruiting, National Cancer Center, Japan | Recruiting --> Active, not recruiting

10 months ago

Enrollment closed • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR4 (Fibroblast growth factor receptor 4) • NTRK (Neurotrophic receptor tyrosine kinase)

EGFR mutation • BRAF mutation • NRAS mutation • BRAF V600 • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR2 N549K • FGFR1 fusion • FGFR3 fusion • FGFR2 P253R • FGFR2 K310R • FGFR3 Y375C • FGFR2 C382R • FGFR2 N549D • FGFR2 N549H • FGFR2 S252W • FGFR2 Y375C • FGFR3 G380R • FGFR3 K650E • FGFR2 W290C

Tasfygo (tasurgratinib)

11ms

Clinicopathological and genetic landscape of plasmablastic lymphoma in Taiwan. (PubMed, Pathol Res Pract)

Deletion of chromosome 13q14 was frequent. The PBL cases in Taiwan showed recurrent mutations involving JAK-STAT, RAS-MAPK, epigenetic regulation, and NOTCH signaling pathways, findings similar to that from the West.

11 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • STAT3 (Signal Transducer And Activator Of Transcription 3) • SDC1 (Syndecan 1) • CD79A (CD79a Molecule) • IRF4 (Interferon regulatory factor 4)

KRAS mutation • NRAS mutation • MYC expression • MYC rearrangement • FGFR3 fusion • STAT3 mutation • Chr del(13)(q14)

11ms

Systematic review and cumulative analysis of clinical properties of BRAF V600E mutations in PLNTY histological samples. (PubMed, Childs Nerv Syst)

These findings indicate that BRAF V600E-positive PLNTY exhibit characteristic clinical presentations but are not necessarily different in treatment responsiveness. Non-BRAF V600E tumors are more commonly associated with young patients.

11 months ago

Review • Journal

BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3)

BRAF V600E • BRAF V600 • FGFR2 mutation • FGFR2 fusion • FGFR3 fusion

11ms

Real world experience of FGFR gene alterations and clinical outcomes in advanced/metastatic urothelial cancer in Japan: MONSTAR-SCREEN database study. (ASCO-GU 2024)

The results showed a similar trend to previous studies, where FGFR GA was reported in approximately 20% of metastatic UC patients. No difference was found in the PFS and the estimated survival rate by FGFR2/3 GA-positive or -negative patients. Our data showed that treatment pressure did not alter the FGFR status commonly.

11 months ago

Real-world evidence • Clinical data • Clinical • BRCA Biomarker • Real-world • Metastases

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • ARID1A (AT-rich interaction domain 1A) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3) • BICC1 (BicC Family RNA Binding Protein 1) • BAIAP2L1 (BAI1 associated protein 2 like 1) • BAIAP2 (BAR/IMD Domain Containing Adaptor Protein 2) • CASP7 (Caspase 7)

FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR3 S249C • FGFR3 Y373C • FGFR3 fusion • FGFR3 G370C • FGFR3 R248C

FoundationOne® Liquid CDx

11ms

Infigratinib versus placebo in patients with resected urothelial cancer (UC) bearing FGFR3 mutation or fusion: Primary DFS analysis from the phase 3, randomized PROOF302 study. (ASCO-GU 2024)

Our failure to accrue sufficient patients to the current trial precludes any definitive conclusions around the role of infigratinib as adjuvant therapy for FGFR3-altered UC. In the process of study conduct, however, we garnered substantial insights that may aid in the development of future precision oncology trials for adjuvant UC. Clinical trial information: NCT04197986.

11 months ago

Clinical • P3 data

FGFR3 (Fibroblast growth factor receptor 3)

FGFR3 mutation • FGFR3 fusion

Truseltiq (infigratinib)

11ms

FGFR3 mutated (FGFR3mut+) urothelial carcinoma of bladder (UCB) or upper tract (UTUC): A comparative genomic landscape study. (ASCO-GU 2024)

THOR trial showed a significant overall survival benefit with erdafitinib (FGFR inhibitor) vs (taxane or vinflunine) in patients (pts) with advanced UCB or UTUC. Although histologically similar, the genomic landscape of FGFR3mut+ UTUC has notable differences with FGFR3mut+ UCB. Limitations include lack of clinical data annotation. The findings may impact of clinical trial designs for UCB and UTUC, including evaluating combinations of anti-FGFR3 with other agents.

11 months ago

Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • MTAP (Methylthioadenosine Phosphorylase) • TSC1 (TSC complex subunit 1) • FUS (FUS RNA Binding Protein)

PD-L1 expression • MSI-H/dMMR • FGFR3 mutation • FGFR3 fusion • HRD signature

PD-L1 IHC 22C3 pharmDx

Balversa (erdafitinib) • Javlor (vinflunine)

11ms

Diffuse Gliomas with FGFR3-TACC3 Fusions: Oncogenic Mechanisms, Hallmarks, and Therapeutic Perspectives. (PubMed, Cancers (Basel))

Several FGFR inhibitors were tested in FGFR3-TACC3 fusion-positive gliomas and proved some efficacy, although inferior to the results seen in other FGFR3-TACC3 fusion-driven cancers. In this review, we summarize and discuss the state-of-the-art knowledge resulting from a 10-year research effort in the field, its clinical implications for glioma patients, the potential reasons for targeted therapy failures, and the perspective of emerging treatments.

11 months ago

Review • Journal

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR3-TACC3 fusion • FGFR3 fusion

12ms

Clinical significance of molecular subgroups of polymorphous low-grade neuroepithelial tumor of the young (PLNTY): A small single institutional case series and integrated analysis. (PubMed, Pathol Res Pract)

Our study suggests that PLNTYs have distinct clinicopathological features and are driven by genetic alterations in the MAPK pathway. The molecular subgroups of PLNTYs share similar findings, but also demonstrate distinct patient demographics.

12 months ago

Journal

BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • CD34 (CD34 molecule) • GFAP (Glial Fibrillary Acidic Protein)

BRAF V600E • BRAF V600 • FGFR2 mutation • FGFR3 fusion