FGFR3 overexpression

P2, N=202, Not yet recruiting, Abbisko Therapeutics Co, Ltd

Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Glabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1/2 phosphorylation and suppression of epithelial-mesenchymal transition (EMT).

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.

While both EPN patients did not respond to erdafitinib treatment, the FGFR1-ITD-harbouring tumour showed a significant decrease in tumour volume and contrast enhancement throughout treatment. The tumour remained stable 6 months after treatment discontinuation.

Background: In view of the efficacy of FGFR targeting in early and advanced bladder cancer, as has been shown for erdafitinib in the THOR and NORSE trial, molecular testing of FGFR mutations and fusions will soon become clinical routine worldwide... PCR-based FGFR assessment by Therascreen and UroTyper is highly concordant and enables fast, local FGFR assessment within few hours. FGFR3 mutations are associated with increased TROP2 & NECTIN4 expression indicating potential synergistic options which warrants further exploration as part of molecularly stratified clinical trials.

Furthermore, medical reports indicated higher rates of recurrence and bleeding intensity among smokers. These findings emphasize the potential role of FGFR3 as a key molecular factor in JNA, particularly in the context of smoking.

The study findings indicate that the intensity and percentage of cell staining for P53 and CK20 in the UCC of the bladder can aid in differentiating the grading patterns. The tendency of tumor relapse can be predicted by demonstrating heterogeneous and non-papillary patterns.

Our results showed that up-regulation of FGFR3 reversed the inhibitory effect of crocin+DDP on the MAPK/ERK signaling pathway. Still, this effect could be counteracted by PD184352, which simultaneously regulated the proliferation, apoptosis, and EMT of AGS cells. In conclusion, crocin, combined with DDP, inhibits proliferation, apoptosis, and EMT of GC through the FRFR3/MAPK/ERK pathway.

In view of the high concordance found between tchRNA-Seq and FISH, our approach could provide additional relevant molecular information and could be useful for the identification of new biomarkers at diagnosis or relapse. The clustering of patients into cytogenetically defined subgroups by studying up- or down-regulated genes could improve the genetic risk stratification. Nevertheless, it is necessary to increase the cohort size to validate these promising results.

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.

Ceritinib is a second-generation ALK-TKI and has shown great efficacy in the treatment of patients with both newly diagnosed and crizotinib (a first-generation ALK-TKI)-refractory ALK-rearranged NSCLC. Amplified cMET counter-activated EGFR and/or Her3, and induced ceritinib resistance. These results reveal multiple ceritinib resistance mechanisms and suggest that ceritinib resistance might be able to overcome by identifying precise resistance mechanisms.

Mutant FGFR3 initiates luminal papillary BCa formation and favors BCa male sex bias, potentially through FGFR3-dependent ESR1 downregulation. Patients with premalignant lesions or early-stage BCa could thus potentially benefit from FGFR3 targeting. FGFR3 expression level in epithelia could account for FGFR3-driven carcinoma tissue specificity.

In preclinical models, we identified the overexpression of Fibroblast Growth Factor Receptor (FGFR) 3 as a molecular mechanism potentially responsible for trastuzumab resistance in GC, providing the rationale for the inhibition of this receptor as a potential second-line strategy in this disease. In this Simon’s two-stages phase 2, single arm, open-label study, adult patients with advanced EGJ/GC refractory to first-line trastuzumab-containing therapies received a starting dose of 13.5 mg oral pemigatinib – an oral inhibitor of FGFR1, 2, and 3 – once daily (21-day cycle; 2 weeks on, 1 week off). These results do not support the therapeutic activity of targeting FGFR in patients with advanced EGJ/ GC refractory to trastuzumab-containing therapies. The combination of treatments targeting HER2 and FGFRs remains a strategy to be potentially explored.

There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Assessment of FGFR mRNA expression identified a high-risk subgroup of patients with mUCa. These patients showing overexpression of FGFR3 mRNA were found to have unfavorable DSS after CPI treatment. Using this approach may be suitable for identifying a patient population with poor response to CPI treatment, which may benefit from early FGFR inhibition.

First-line treatment with the RP2D of R+A achieved favorable clinical efficacy and tolerability in pts with cisplatin-ineligible, metastatic UC characterized by high FGFR1/3 mRNA expression and generally low/negative PD-L1 expression . Encouraging efficacy was observed regardless of PD-L1 expression or FGFR3 mutation status, warranting future investigation.

FGFR3 IHC is a useful screening tool for the detection of FGFR3 alterations and could be included in the workflow for isocitrate dehydrogenase (IDH) wild-type glioma diagnostics. Samples with positive FGFR3 staining could then be selected for NGS-based diagnostic tools.

In conclusion, FGFR3 overexpression enhances DDP-resistance of ovarian cancer by promoting EGFR phosphorylation and further activating PI3K/AKT pathway. This study may offer promising targets for DDP-resistant ovarian cancer.

Genomic alterations in MIBC revealed in TCGA data also concern NMIBC and seem to be associated with prognosis in terms of recurrence and progression. Correcting these alterations by targeted therapies seems a promising pharmacological approach.

A mUCB high-risk group with FGFR3-mRNA overexpression could be identified, which shows a lower CSS despite OK. Standardized, locally available FGFR mRNA analyzes could identify an FGFR inhibitor target population that is twice as large as the population that is only detected by FGFR alterations.

CRC2017_02. 2017-004522-14.

In this report, we found that these FGFR3 mutations were associated with favorable features and prognosis of bladder cancer compared with patients with FGFR3 overexpressed tumors only. As a consequence, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with FGFR3 protein overexpression only.

The assessment of FGFR mRNA by standardized RT-qPCR identified a high risk UCB patient cohort, which does have inferior disease specific survival despite IO treatment and does over express FGFR3 mRNA. The assessment of FGFR mRNA levels by using this standardized, locally applicable FGFR testing could identify an FGFR inhibitor target population with poor response to IO treatment which is twice the size as currently detected by FGFR genomic alterations alone.