FGFR2 expression

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.

Pharmacokinetic evaluations demonstrated 7k's favorable properties, and xenograft models evidenced its notable anti-melanoma efficacy, achieving a TGI of 73%. These results highlighted DHPS as key in melanoma VM formation and confirmed 7k's potential as a novel anti-melanoma agent.

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.

Results demonstrated that Trimer-pep conjugated with DOX showed the highest permeation, while the ACSAG conjugate also demonstrated reasonable permeation of the drug. These results indicate that these peptides may be further explored and potentially utilized to create drug conjugates for targeting tumor cells expressing FGFR2 for developing therapeutics.

FDA approval of zolbetuximab's, an anti-CLDN18.2monoclonal antibody, is expected soon. Additionally, bemarituzumab, ananti-FGFR2b monoclonal antibody, has shown improvements in combination withchemotherapy in those with HER2 negative GAC with FGFR2 overexpression...Lastly, TROP-2 has emergedas an exciting solid tumor target and study is expected in GAC. All three ofthese therapeutic targets have seen an abundance of drug development in recentyears, and we anticipate newer targeted agents driving therapeutic decisions inGAC in the coming years.

This study revealed the unknown role of FGFR2 signalling in activation of autophagy and regulation of the p62/Keap1/Nrf-2 interdependence, which has a negative impact on the response of ER+ BCa cells to anti-ER therapies. The data from in silico analyses suggest that expression of Nrf-2 could act as a marker indicating potential benefits of implementation of anti-FGFR therapy in patients with ER+ BCa, in particular, when used in combination with anti-ER drugs.

In conclusion, CAFs inhibited ferroptosis to decrease DDP sensitivity in NPC through secreting FGF5 and activating downstream FGFR2/Nrf2 signaling. The therapeutic strategy targeting FGF5/FGFR2 axis from CAFs might augment DDP sensitivity, thus decreasing the side effects of DDP in NPC treatment.

FGFR2::BICC fusion was detected in a case of cHCC-CCAs. FGFR2 genetic alterations may be prevalent in cHCC-CCAs as well as small duct-type iCCAs, which suggest cHCC-CCAs may also be a possible therapeutic target of FGFR2 inhibitors.

P=N/A, N=120, Active, not recruiting, Weill Medical College of Cornell University | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

Decreased expression of miR-889-3p in OSCC tumours suggests that miR-889-3p functions as a tumour suppressor gene. Overexpression of FGFR2 further proves the role of miR-889-3p in the regulation of the FGFR2 pathway. This was further confirmed by showing differences in miR-889-3p expression in positive and negative LNM cases.

This last finding entails that also this setting of patients could benefit from FGFR targeted therapies, widening indication of these drugs for iCCA patients beyond current approval. Future clinical studies are therefore encouraged to confirm this hypothesis.

All patients received carboplatin and paclitaxel given every three weeks for six cycles and were randomized to bevacizumab. An FGFR/FGF-based gene signature identified in our study appears to predict long-term benefit from bevacizumab. This observation is hypothesis-generating and requires validation on independent cohorts.

In this single-arm, multi-center, phase 2 study, eligible patients had metastatic untreated HER2-negative gastric adenocarcinoma with centrally confirmed expression of PD-L1 (CPS≥5; DAKO 28-8) and FGFR2 (moderate (2+) and strong (3+) membranous staining in more than 1% of tumor cells; Abсam EPR24075-418). Patients received nivolumab 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks... An interim analysis demonstrates modest efficacy and an acceptable safety profile of nivolumab in combination with chemotherapy in patients with FGFR2-positive, PD-L1-positive metastatic GC. Further follow-up is ongoing. 1.

Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%-2.6% and 1.5%-2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib.

FGFR2 expression was detected in cHCC-CCAs as frequently as small duct-type iCCAs. This finding suggests a possible therapeutic indication of FGFR2 inhibitors for the patients with cHCC-CCAs.

FISH achieved satisfactory concordance with NGS, has potential value for FGFR2 screening for targeted therapies. FGFR2 detection should be prioritized for unique clinical subgroups in ICC, which features a histological small duct subtype, early clinical stage, and reduced mucus production.

Comparative analysis of RNA-sequencing data of FGFR1 and FGFR2 knockdown glioblastoma cells revealed a FGFR1-specific gene regulatory network associated with tumor invasion. Our study reveals new gene candidates linked to FGFR1-mediated glioblastoma invasion.

Moreover, TAX evidently inhibited the tumor growth in nude mice and the expression of c-Myc, cyclin D1, p-AKT and FGFR2 were down-regulated in xenograft tumor. These results indicate that TAX suppresses the proliferation of androgen-independent PCa cells via inhibiting the activation of PI3K/AKT signaling pathway and the expression of FGFR2, which means TAX may be a novel anti-tumor agent for later PCa treatment.

In depth spatial in situ sequencing showed potential to provide a deeper understanding of the underlying mechanisms involved in the recurrence of disease and revealed novel potential predictive biomarkers for disease relapse in colon cancer stage II patients. Our open-access GTC-tool allowed us to accurately capture the tumour compartment and quantify spatial gene expression in colon cancer tissue.

FGF10/FGFR2 activates the Akt/mTOR and VEGF/Slug pathways, which are associated with the stimulation of migration and invasion in CCA. Moreover, the FGF10/FGFR2 signaling was inhibited by an FGFR inhibitor resulting suppression of cell migration, which warrants further studies on their clinical utility for CCA treatment.

The expression of FGFR2, and its isoforms, relate to breast cancer subtypes. FGFR2 expression is related to maintaining epithelial characteristics of breast cancer whereas low FGFR2 is associated with more aggressive, basal forms.

Clone EPR24075-418 showed the best result in assessing the expression of FGFR2: the correlation with FISH results in reaction 3+ was 100%. Due to the high heterogeneity of FGFR2 expression, it is recommended to either examine the material of the primary tumor and metastasis, or evaluate a large volume of the primary tumor.

P2; N=23; Recruiting; Sponsor:Kidney Cancer Research Bureau

Animal experiments on a carbon tetrachloride (CCl) mouse model and a nonalcoholic steatohepatitis mouse model indicate that CYN treatment reduces liver fibrosis during fibrosis formation. These findings suggest that CYN prevents liver fibrosis formation at the cell level and in mouse models.

The study identified dysregulated genes related to cancer pathways in CC patients suggesting cancer risk. The findings suggest that the elevated expression of FGFR2 and CEBPB in liver may contribute to cancer development in CC patients.

In vivo studies using patient-derived xenograft (PDX) models of high-risk NB (MYCN-amplified and ALKF1174L mutant) showed that combinations of either ponatinib or erdafitinib with lorlatinib decreased tumour growth and increased survival compared to PDXs treated with vehicle or either agent alone. In conclusion, these findings suggest that FGFR2 alters NB sensitivity to lorlatinib and modulation of this pathway in combination with ALK inhibition is a promising approach to improve NB treatment response and ultimately patient survival.

NXP800, a HSF1 inhibitor, demonstrated significant therapeutic activity in a cholangiocarcinoma PDX. Further studies are needed and being performed to determine the role of HSF1 inhibition in human cholangiocarcinoma.

Moreover, the combination of a PAI-1 inhibitor and anti-PD-1 therapy exhibited superior antitumor activity in mice. These findings offer novel insights into the molecular mechanisms underlying tumor deterioration and provide potential therapeutic targets for CRC treatment.

Background and Aim: FGFR2 fusion gene alteration has observed in 15-20% of intrahepatic cholangiocarcinoma (iCCA), and anti-FGFR inhibitor, Pemigatinib, is commercially available to patients who have FGFR2 alteration. Combination administration of anti-FGFR inhibitor and GEM showed synergistic effect to the FGF activated iCCA cell line. 1001

DZB inhibited growth of three tumor xenograft models with reported expression or amplification of CSF1R, whereas the specific FGFRi, pemigatinib, had no efficacy. Similar modulation of the tumor microenvironment was observed in an FGFR-insensitive syngeneic bladder model, MBT-2. These data confirm CSF1R as an important oncology target for DZB and provide mechanistic insight for the ongoing clinical trials, in which DZB is combined with the PD-L1 antibody, atezolizumab.

Knockout of RBM34 significantly inhibited cell proliferation, migration, and xenograft tumor growth, and sensitized HCC cells to sorafenib treatment. RBM34 inhibition reduced FGFR2 expression and affected PI3K-AKT pathway activation in HCC cells. Our study suggests that RBM34 may serve as a new prognostic marker and therapeutic target of HCC.

We demonstrated that FGFR2 high expression was the independent prognostic factor for recurrence of resected ICC.

Pairwise comparison of 4 tests based on the same patient population was performed: 3 IHC assays [Abcam clone EPR24075-418, R&D clone 98706, Santa Cruz clone C-8] and one FISH test... Among patients who were negative by FISH, 86%-93% of the patients were negative by IHC assay (Abcam). Among patients who were positive by FISH, 75-80% of them were positive by IHC. FISH should not be recommended as a substitute for a FGFR2 IHC assay due to high probability of false negative prediction as a result of intratumoral heterogeneity and low PCC.

FGFR2 is overexpressed in one third of patients, and its targeting with a specific monoclonal antibody bemarituzumab showed a significant improvement in survival...The combination of zolbetuximab and chemotherapy provides a survival benefit, correlated with the intensity of CLDN 18.2 expression...Finally, with the recent advent of immunotherapy, one of the future challenges will be to optimize it through combination strategies with targeted therapies. The combination of anti-angiogenic and immunotherapy seems promising in gastric cancer.

FGFR1 and FGFR2 may participate in the occurrence of SCC of the throat: (I) positive FGFR1 and FGFR2 expressions are not associated with gender, age, smoking history, alcohol consumption history, tumor diameter, lymph node metastasis, degree of differentiation, or TNM stage. (II) FGFR2 increases successively with higher FGFR1 expression and with a positive correlation in laryngeal SCC.

In multivariable Cox regression analyses, tumors with FGFR2b+/FGFR2c- expression were significantly associated with longer DSS (HR 0.37; 95% CI 0.153-0.872; log-rank p < 0.023) compared to FGFR2b-/FGFR2c+ tumors. In conclusion, FGFR2b+/FGFR2c- expression is associated with favorable clinicopathologic markers and clinical outcomes suggesting that FGFR2b could play a role in tailoring the management of EEC patients in the clinic if these findings are confirmed in an independent cohort.

FGFR mRNA overexpression occurs frequently in cholangiocarcinoma in the absence of genetic FGFR alterations. This study identifies a molecular subpopulation in cholangiocarcinoma for which further investigation of FGFR inhibitors is merited outside currently approved indications.