News - FGFR3-TACC3 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

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)

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

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

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

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

1year

Optimizing the role of the advanced practice provider in the management of a single patient investigational new drug (IND) (SNO 2023)

Extended genomic profiling of his tumor at time of biopsy revealed a FGFR3-TACC3 fusion and MGMT promoter methylation, and the decision was made to pursue a single patient IND for anlotinib for use in combination with temozolomide. As first point of contact for the patient and family, the APP plays a key role in glioma research within the multidisciplinary team by providing ongoing symptom management, education, and monitoring for patients receiving investigational drugs.

1 year ago

Clinical • IND • Metastases

FGFR3 (Fibroblast growth factor receptor 3) • MGMT (6-O-methylguanine-DNA methyltransferase) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR3-TACC3 fusion • MGMT promoter methylation • FGFR3 fusion

Focus V (anlotinib) • temozolomide

1year

FGFR alterations in gliomas; clinical, radiographic and molecular characterization (SNO 2023)

FGFR3-TACC3 fusions (F3T3) gliomas represent a unique entity among IDH WT gliomas. In our cohort, 100% of the patients with F3T3-positive glioblastomas also had an associated TERT promoter mutation. To our knowledge, this is one of the larger cohorts showing the association between FGFR3 and TERT promoter alterations in glioblastomas.

1 year ago

Clinical

FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • TERT (Telomerase Reverse Transcriptase) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • LMNB2 (Lamin B2)

FGFR3-TACC3 fusion • FGFR mutation • CDKN2A mutation • FGFR fusion • FGFR3 fusion • TERT mutation • IDH wild-type • TERT promoter mutation • FGFR3 amplification

1year

Targeting FGFR fusions: a case of catequentinib (AL3818) and temozolomide combination therapy for recurrent MGMT methylated TACC-FGFR fusion positive glioblastoma (SNO 2023)

Catequentinib in combination with metronomic temozolomide was well tolerated in this single patient. This patient’s response shows the promise of intentional, patient-specific care at the intersection of molecular testing and rational drug design. The patient will continue therapy and updated clinical and radiographic outcomes will be presented.

1 year ago

Clinical • Combination therapy

FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor) • MGMT (6-O-methylguanine-DNA methyltransferase) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR3-TACC3 fusion • MGMT promoter methylation • FGFR fusion • FGFR3 fusion

Focus V (anlotinib) • temozolomide

1year

Molecular profiling and actionable mutations in adult patients with IDH wild type gliomas and glioneuronal and neuronal tumors (SNO 2023)

Three patients recurred after first-line therapy: 1 with BRAF mutated GBM, 1 with GBM harboring FGFR3-TACC3 fusion, and 1 with NTRK1 fusion positive glioneuronal tumor received specific BRAF/MEK inhibitor (dabrafenib/trametinib), FGFR inhibitor (pemigatinib), and NTRK inhibitor (larotrectinib), respectively. The incidence of actionable molecular alterations in IDH wt gliomas and glioneuronal/neuronal tumors was low. However, the use of targeted therapies may lead to significant impact on the outcome.

1 year ago

Clinical

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR3 (Fibroblast growth factor receptor 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • KRAS mutation • PIK3CA mutation • BRAF V600 • NTRK1 fusion • KIT mutation • FGFR3-TACC3 fusion • MET mutation • FGFR3 fusion • IDH wild-type • NTRK1 positive

Mekinist (trametinib) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Pemazyre (pemigatinib)

1year

FGFR alterations in gliomas; clinical, radiographic and molecular characterization (SNO 2023)

1 year ago

Clinical

FGFR3-TACC3 fusion • FGFR mutation • CDKN2A mutation • FGFR fusion • FGFR3 fusion • TERT mutation • IDH wild-type • TERT promoter mutation • FGFR3 amplification

over1year

FIND: A phase II study to evaluate the efficacy of erdafitinib in FGFR-altered NSCLC (ESMO 2023)

Conclusions According to the first stage results of the two-stage Simon's design, erdafitinib showed preliminary efficacy in NSCLC with FGFR translocations. Further molecular, pharmacological and clinical data are needed to evaluate the efficacy of FGFR inhibition in NSCLC, especially in pts with FGFR mutations.

over 1 year ago

Clinical • P2 data

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

FGFR3-TACC3 fusion • FGFR mutation • FGFR3 fusion

Balversa (erdafitinib)

over1year

Glioblastoma with FGFR3-TACC3 fusion and TERT promoter mutation: A case report and review of the literature (AANP 2023)

Conclusions IDH wild-type glioblastomas have a poor prognosis. Identifying patients with FGFR3-TACC3 fusion can potentially provide a targeted treatment.

over 1 year ago

Clinical • Review

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

FGFR3-TACC3 fusion • FGFR3 mutation • FGFR fusion • FGFR3 fusion • TERT mutation • IDH wild-type • TERT promoter mutation

over1year

Evaluating the use of circulating tumor DNA (ctDNA) in patients with urothelial cancer in the context of FGFR-targeted therapy. (ASCO 2023)

This ongoing study suggests cfDNA is a valuable minimally invasive adjunct to tissue-based assays for the detection of FGFR alterations to identify patients for FGFR inhibitor therapy and to monitor for mechanisms of resistance.

over 1 year ago

Clinical • Circulating tumor DNA

FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR3-TACC3 fusion • FGFR3 mutation • FGFR1 mutation • FGFR3 S249C • FGFR1 fusion • FGFR3 fusion • FGFR wild-type

Balversa (erdafitinib)

over1year

AMB302/GR1017, an antibody-drug conjugate (ADC) with topoisomerase 1 inhibitor shows therapeutic potency in orthotopic glioblastoma PDX and bladder cancer models with FGFR3-TACC3 fusion (AACR 2023)

AMB302/GR1017 showed robust anti-tumor efficacies in F3-T3 fusion and FGFR3 overexpression models derived from GBM and BC in vitro and in vivo. In addition, AMB302/GR1017 was well tolerated with no adverse effects in rodent model. Our data suggest AMB302/GR1017 has a potential therapeutic option as a first-in-class FGFR3 targeting ADC for GBM, BC, and other solid tumors with FGFR3 overexpression or alterations.

over 1 year ago

Preclinical

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

FGFR3-TACC3 fusion • FGFR3 overexpression • FGFR3 fusion • FGFR3 amplification • FGF3 overexpression

AMB302

almost2years

Oncogenic driver FGFR3-TACC3 requires five coiled-coil heptads for activation and disulfide bond formation for stability. (PubMed, Oncotarget)

These results demonstrate that clinically identified FGFR3-TACC3 fusion proteins differ in their biological activity, depending upon the specific breakpoint. This study further suggests the TACC3 dimerization domain of FGFR3-TACC3 as a novel target in treating FGFR translocation driven cancers.

almost 2 years ago

Journal

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

FGFR3-TACC3 fusion • FGFR3 fusion

almost2years

Clinico-pathological and epigenetic heterogeneity of diffuse gliomas with FGFR3::TACC3 fusion. (PubMed, Acta Neuropathol Commun)

Among gliomas with FGFR3::TACC3 fusion, age, TERT promoter mutation, pathological features, DNA-methylation profiling and fusion subtype are of interest to determine patients' risk.

almost 2 years ago

Journal

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

FGFR3-TACC3 fusion • FGFR3 mutation • FGFR3 fusion • TERT mutation • IDH wild-type • TERT promoter mutation

almost2years

Efficacy and safety of derazantinib (DZB) in patients with metastatic urothelial carcinoma (mUC) with activating FGFR1/2/3 genetic aberrations (GA): Results from the phase 1b/2 FIDES-02 study. (ASCO-GU 2023)

Derazantinib showed signals of clinical activity in some patients with mUC and FGFR1-3 GA but the observed ORR and PFS did not meet contemporary benchmarks that would support further clinical development of derazantinib as monotherapy in this indication. Derazantinib showed a well-manageable safety profile with low rates of hand-foot syndrome, stomatitis, nail toxicity and retinal side effects. Clinical trial information: NCT04045613.

almost 2 years ago

Clinical • P1/2 data • Metastases

FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • TACC3 (Transforming acidic coiled-coil containing protein 3)

FGFR2 mutation • FGFR3-TACC3 fusion • FGFR2 fusion • FGFR3 mutation • FGFR1 mutation • FGFR3 S249C • FGFR1 fusion • FGFR3 fusion

derazantinib (ARQ 087)

almost2years

Clinicopathological and Molecular Characteristics of Glioblastoma, IDH-wildtype with FGFR3-TACC3 Fusions: A Single Institution Experience with 25 cases (USCAP 2023)

We demonstrated that glioblastomas with F3T3 fusion were peculiar molecular subgroup of IDH-wildtype glioblastoma with female preference and relatively located in subcortical region with well-demarcated. Curvilinear capillary proliferation is the most characteristic morphological feature and CDKN2A deletion was accompanied in half of the cases.

almost 2 years ago

Clinical

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) • TERT (Telomerase Reverse Transcriptase) • TACC3 (Transforming acidic coiled-coil containing protein 3) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)

TP53 mutation • EGFR amplification • PTEN mutation • FGFR3-TACC3 fusion • MDM2 amplification • CDKN2A deletion • CDK4 amplification • FGFR3 fusion • TERT mutation • IDH wild-type • TERT promoter mutation • CDK4 mutation

almost2years

Infiltrating gliomas with FGFR alterations: Histologic features, genetic alterations, and potential clinical implications. (PubMed, Cancer Biomark)

Histologic features correlate with FGFR alterations in IGs. FGFR3-TACC3 fusion and FGFR3 amplification are the most common FGFR alterations in IGs. FGFR alterations are a rare, but potentially viable, therapeutic target in asubset of IGs.

almost 2 years 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) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • PTEN mutation • FGFR3-TACC3 fusion • FGFR mutation • FGFR3 fusion • IDH wild-type • FGFR3 amplification

almost2years

Varied histomorphology and clinical outcomes of FGFR3-TACC3 fusion gliomas. (PubMed, Neurosurg Focus)

One patient received erdafitinib, a targeted FGFR inhibitor, for 3 months at late disease recurrence and no response was seen...However, further research is needed to examine whether IDH1/2-wild-type tumors with FGFR3-TACC3 fusion should be classified as a subtype on the basis of this molecular fusion. Because patients with IDH1/2-wild-type GBM with FGFR3-TACC3 fusion have improved survival, routine molecular testing for this mutation in patients enrolled in clinical trials and subsequent stratification may be warranted.

almost 2 years ago

Clinical data • Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

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

Balversa (erdafitinib)

2years

FGFR3-TACCs3 Fusions and Their Clinical Relevance in Human Glioblastoma. (PubMed, Int J Mol Sci)

The subgroup of FGFR3-TACC3 fusion-positive glioblastomas presents with recurrent clinical and histomolecular characteristics, defining a distinctive subtype of IDH-wildtype glioblastoma. This review aims to provide an overview of the available literature on FGFR3-TACC3 fusions in glioblastoma and possible implications for actual clinical practice.

2 years ago

Review • Journal

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

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

over2years

Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study. (PubMed, Clin Cancer Res)

FGFR inhibitor monotherapy with infigratinib had limited efficacy in a population of patients with recurrent gliomas and different FGFR genetic alterations, but durable disease control lasting more than 1 year was observed in patients with tumors harboring FGFR1 or FGFR3 point mutations or FGFR3‑TACC3 fusions. A follow-up study with refined biomarker inclusion criteria and centralized FGFR testing is warranted.

over 2 years ago

P2 data • Journal

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

FGFR3-TACC3 fusion • FGFR3 mutation • FGFR1 fusion • FGFR3 fusion • FGFR3 K650E

Truseltiq (infigratinib)

over2years

FGFR Fusions as an Acquired Resistance Mechanism Following Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) and a Suggested Novel Target in Advanced Non-Small Cell Lung Cancer (aNSCLC). (PubMed, J Clin Med)

Over 23% of FGFR2/3 fusions in aNSCLC may be associated with acquired resistance following treatment with EGFR TKIs. In this clinical scenario, a combination of EGFR TKIs and FGFR TKIs represents a promising treatment strategy.

over 2 years ago

Preclinical • Journal

EGFR (Epidermal growth factor receptor) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • FGFR2 mutation • FGFR3-TACC3 fusion • FGFR2 fusion • EGFR L861Q • FGFR fusion • FGFR1 fusion

Balversa (erdafitinib)

over2years

DNA methylation analysis of glioblastomas harboring FGFR3-TACC3 fusions identifies a methylation subclass with better patient survival. (PubMed, Acta Neuropathol)

No abstract available

over 2 years ago

Journal • Epigenetic controller

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

FGFR3-TACC3 fusion • FGFR3 fusion

over2years

Dual targeting of FGFR3 and ERBB3 enhances the efficacy of FGFR inhibitors in FGFR3 fusion-driven bladder cancer. (PubMed, BMC Cancer)

We demonstrate that increased expression of pERBB3 is a key mechanism of adaptive resistance to FGFR inhibitors in FGFR3-fusion driven bladder cancers, and that this also occurs rapidly following FGFR inhibitor treatment. Our findings demonstrate that resistance can be overcome by combination treatment with a pan-ERBB inhibitor and suggest that upfront combination treatment with FGFR and pan-ERBB inhibitors warrants further investigation for FGFR3-fusion harbouring bladder cancers.

over 2 years ago

Journal

FGFR3 (Fibroblast growth factor receptor 3) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • BAIAP2L1 (BAI1 associated protein 2 like 1)

FGFR3-TACC3 fusion • FGFR3 fusion • FGFR3-BAIAP2L1 fusion

Mekinist (trametinib) • Balversa (erdafitinib) • Truseltiq (infigratinib) • Lytgobi (futibatinib) • sapitinib (AZD8931)

over2years

A cell-free RNA-based next-generation sequencing (NGS) assay for the detection of actionable gene fusions in patients with non–small cell lung cancer (NSCLC). (ASCO 2022)

This novel cfRNA assay can detect actionable gene fusions and exon skipping events in liquid biopsies with high sensitivity. Combining cfRNA with more routine cfDNA testing can increase the total actionable diagnostic information from non-invasive testing in NSCLC patients where tissue samples are lacking, especially for gene fusions not amenable to detection in cfDNA.

over 2 years ago

Clinical • Next-generation sequencing

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) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • TACC3 (Transforming acidic coiled-coil containing protein 3)

MET exon 14 mutation • FGFR3-TACC3 fusion • FGFR2 fusion • ALK fusion • NRG1 fusion • FGFR3 fusion

LiquidHALLMARK®

over2years

HSP90-CDC37 functions as a chaperone for the oncogenic FGFR3-TACC3 fusion. (PubMed, Mol Ther)

Notably, F3-T3 was found to be highly expressed in both untreated and matched recurrence glioblastoma under the concurrent radiotherapy and temozolomide (TMZ) treatment, suggesting that targeting F3-T3 is a valid strategy for treatment...HSP90 inhibitors sensitized F3-T3 glioma cells to TMZ via inhibition of F3-T3 activation and potentiated TMZ-induced DNA damage. These results demonstrate that F3-T3 oncogenic function is dependent on the HSP90 chaperone system and suggests a new clinical option for targeting this genetic aberration in cancer.

over 2 years ago

Journal

FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

FGFR3-TACC3 fusion • FGFR3 fusion

temozolomide

over2years

Interim Results from a Phase 1b Clinical Trial Evaluating Tolerability and Activity of FGFR Inhibition in Localized Upper Tract Urothelial Carcinoma (UTUC) (AUA 2022)

Conclusions : Infigratinib shows substantial activity in patients with localized UTUC bearing FGFR3 mutations, consistent with previous data in the metastatic setting. Enrollment continues, and based on these promising initial results, a phase 2 expansion evaluating additional cycles is planned.

over 2 years ago

Clinical • P1 data • Late-breaking abstract

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

FGFR3-TACC3 fusion • FGFR3 mutation • FGFR3 fusion

Truseltiq (infigratinib)

over2years

The spectrum of FGFR mutations in pediatric and young adult solid tumor (AACR 2022)

The majority of the FGFR-positive tumors are low-grade CNS tumors. Further, the identification of FGFR alterations can significantly improve the tumor diagnosis and provide genomic evidence for potential targeted treatment with FGFR inhibitors.

over 2 years ago

Clinical

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • NF1 (Neurofibromin 1) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3) • FGFR4 (Fibroblast growth factor receptor 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)

FGFR2 mutation • FGFR3-TACC3 fusion • FGFR2 fusion • FGFR mutation • FGFR1 fusion • FGFR3 fusion • FGFR1-TACC1 fusion

over2years

Analytical concordance of 3 independent diagnostic assays for the detection of FGFR alterations in urothelial carcinoma tumor tissue (AACR 2022)

There was a high level of analytical concordance in detection of FGFR alterations indicated for erdafitinib between the Qiagen companion diagnostic assay and 2 commercially available NGS platforms. >

over 2 years ago

Diagnostic assay

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

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

TruSight Oncology 500 Assay • therascreen® FGFR RGQ RT-PCR Kit

Balversa (erdafitinib)

over2years

Glioblastoma, IDH-Wild Type With FGFR3-TACC3 Fusion: When Morphology May Reliably Predict the Molecular Profile of a Tumor. A Case Report and Literature Review. (PubMed, Front Neurol)

Based on this unusual morphology, molecular analyses were performed and an FGFR3 exon17-TACC3 exon 10 fusion was found. The present case contributes to widening the morphologic spectrum of FGFR3-TACC3-fused GBM, IDHwt and emphasizes that pathologists, in the presence of a GBM, IDHwt with unconventional morphology, should promptly search for this fusion gene.

over 2 years ago

Review • Journal

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

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

almost3years

Targeting gene fusions in glioma. (PubMed, Curr Opin Neurol)

Increasing detection of gene fusions in glioma along with basket trials have helped define different fusion phenotypes and paved the way for targeted kinase inhibitor-based therapies. Targeting NTRK fusions has been the most successful fusion-guided therapy to date and evaluating all patients for these fusions may be warranted.

almost 3 years ago

Journal

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

FGFR3-TACC3 fusion • FGFR3 fusion • MET fusion • NTRK fusion

almost3years

Polymorphous low-grade neuroepithelial tumor of the young with FGFR3-TACC3 fusion mimicking high-grade glioma: Case report and series of high-grade correlates (SNO 2021)

CONCLUSIONS PLNTY is a rare low-grade entity that can display characteristics of high-grade glioma, particularly in adults. The potential for a unique entity mimicking PLNTY which may act as a precursor lesion for a more malignant phenotype should be considered in cases with FGFR3-TACC3 fusions and other high-grade features.

almost 3 years ago

Clinical

FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CD34 (CD34 molecule)

FGFR3-TACC3 fusion • MGMT promoter methylation • FGFR3 fusion • TERT mutation • TERT promoter mutation

3years

Differences in genomic profile of high-grade urothelial carcinoma according to tumor location. (PubMed, Urol Oncol)

Despite the small cohort size, we identified genetic differences between UTUC and BLUC in Korean patients by NGS. An understanding of the comprehensive molecular characteristics of UTUC and BLUC may be helpful in detecting candidates for targeted therapy.

3 years 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) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • TERT (Telomerase Reverse Transcriptase) • ASXL1 (ASXL Transcriptional Regulator 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • KDM6A (Lysine Demethylase 6A) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)

TP53 mutation • ARID1A mutation • FGFR3-TACC3 fusion • FGFR2 fusion • ERBB3 mutation • FGFR3 fusion • TERT mutation • TERT promoter mutation