FGFR2 (Fibroblast growth factor receptor 2)

Although the addition of modified FOLFOX (fluorouracil, leucovorin, and oxaliplatin) to active symptom control improved the overall survival of patients with progressing advanced BTC despite gemcitabine plus cisplatin treatment, its efficacy was modest. This review delineates the evolution of systemic therapies in patients with pretreated advanced BTC. By examining past developments and recent advances through prospective trials, it highlights novel approaches that may improve outcomes in this challenging disease.

Furthermore, FGFR2 collaborated with EGFR and dual blockade of these receptor signaling pathways significantly reduced mutant KRAS-induced pre-cancerous lesion formation. Together, these data have uncovered a pivotal role for FGFR2 in the early phases of pancreatic tumorigenesis, paving the way for future therapeutic applications of FGFR2 inhibitors for pancreatic cancer interception.

This review also emphasizes the importance of collaborative efforts between clinicians, pathologists, and oncologists to optimize outcomes. By synthesizing the latest molecular insights and treatment trends, this review provides a valuable resource to guide the personalized management of HCC and CCA.

P=N/A, N=100, Recruiting, The Walter and Eliza Hall Institute of Medical Research

Using "CCMN" as an entity would entail mixed repercussions in diagnostic practice, and how and whether it should be used in diagnosis requires deliberate discussion. The concept might bring some benefits, but it may cause more confusion because it would substantially restructure the conventional framework by drawing a boundary within the chondroma and conflating the chondroma with chondroid tenosynovial giant cell tumor.

P1/2, N=407, Completed, Taiho Oncology, Inc. | Trial completion date: May 2021 --> Oct 2024

The combination of DGY-09-192 and the ERα degrader fulvestrant resulted in complete cell growth arrest and tumor regression of ER+/FGFR1-amplified patients-derived xenografts...Treatment with DGY-09-192 resulted in the degradation of mutant FGFR1/2 and blocked mutant receptor-induced signal transduction and antiestrogen resistance. Collectively, our study suggests that degradation of FGFR1/2, in combination with antiestrogens, can be leveraged as a therapeutic strategy in ER+ breast cancers harboring FGFR1/2 driver alterations.

Mechanistically, COPA knockout increases the degradation of leucine-rich pentatricopeptide repeat containing (LRPPRC) protein, leading to reduced inhibitor of DNA binding 3 (ID3) mRNA stability in an m6A-dependent manner. Collectively, these findings reveal a novel mechanism of erdafitinib resistance, providing a potential therapeutic target for FGFR-altered bladder cancer.

Higher expression of FGFR2 and c-Met is associated with more advanced stage, deeper myometrial invasion and lymph node metastasis in endometrial cancer and poorer prognosis. In addition, high expression of FGFR2 is correlated with high c-Met expression.

NSMP molecular group constitutes the majority of clinically low-risk EC patients with isolated local recurrences. The CTNNB1 alteration was validated as a biomarker in prognostication in this independent cohort and may help guide adjuvant treatment decisions.

Our results demonstrated that esrp1 and its paralog esrp2 are expressed in the zebrafish inner ear, and that esrp1/esrp2 double knockout compromised the mechano-electrical transduction (MET) function of hair cells. Additionally, we successfully identified tmc1 and tmc2a mRNAs as the targets of Esrp1/2, which encode essential subunits of the MET complex.

MGACA is a rare breast carcinoma, with distinct morphological, immunohistochemical and molecular features. Most MGACA were BLIS molecular subtype of TNBC. TP53 and BRCA1 gene mutation and MYC gene amplification were the most common genetic changes in MGACA.

These novel DR cervical cancer cells are a critical tool for understanding the molecular mechanisms underpinning drug resistance and for the identification of potential cervical cancer biomarkers. Moreover, the availability of such DR cell lines may facilitate the development of more effective therapeutic strategies using FGFR inhibitors in combination with other agents that target pathways responsible for acquired resistance to FGFR inhibitors.

The cell cycle inhibitory proteins p53 and p21 were significantly upregulated upon treatment with compounds 9 and 20. The docking results revealed that compound 9 exhibits stronger binding affinity to CDK-2 than indirubin, and compound 20 showed a similar binding mode to sorafenib with VEGFR-2.

Deficiency of ARID1A causes abnormalities in the STAT3 pathway, which is one of the downstream pathways of FGFR2, but suppression of USP8 attenuates phosphorylation of STAT3 pT705 and induces apoptosis. Taken together, our data suggest that USP8 is a novel therapeutic target for ARID1A-deficient OCCC and that USP8 inhibitors suppress FGFR2-STAT3 signaling.

This study revealed that different algorithms and design panels for mutation filtering affect the TMB test results. When the TMB result is near the 10 mut/Mb threshold, different methods may yield different results. Moreover, a single test result can affect clinical treatment decisions. Therefore, it is recommended to use TO or TC combined with other tests for evaluating somatic mutations.

P=N/A, N=111, Completed, Weill Medical College of Cornell University | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Oct 2024 | Trial primary completion date: Dec 2025 --> Oct 2024

Moreover, treatment with either an AKT3 inhibitor or an FGFR2 inhibitor significantly attenuates tumor progression in patient-derived xenograft models. Our findings highlight AKT3 and FGFR2 as potential therapeutic targets and prognostic biomarkers, providing valuable insights for the development of rational targeted therapies and immunotherapeutic strategies.

We find new patterns and recapitulate previously reported relationships between regulator and gene-expression, such as CNV-predicted FGFR2 expression and SNP-predicted TP63 expression. Together, iModEst offers an interactive, comprehensive atlas of individual regulator-gene-tissue expression relationships as well as relationships between regulators.

The approval was based on the positive results of an open-label, single-arm, multicenter, phase II study conducted in Japan and China. This article summarizes the milestones in the development of tasurgratinib succinate leading to this first approval for biliary tract cancer.

P2, N=115, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Nov 2024

Recognizing the clinical significance of these alterations, ivosidenib and pemigatinib have been approved in Korea for BTC patients with IDH1 mutations and FGFR2 fusions, respectively. This review explores the epidemiology, risk factors, and molecular features of BTC, along with corresponding targeted therapies. Furthermore, we compare the unique characteristics of BTC in Korea with global data to inform future research and clinical practice.

The high prevalence of BRAF V600E mutations, particularly in mandibular AMs, suggests its potential as a diagnostic and therapeutic target. Distinct mutation profiles between maxillary and mandibular AMs indicate molecular diversity. In BRAF-negative cases, alternative oncogenic pathways involving SMO, FGFR2, and RAS may be actionable targets, underscoring the need for personalized treatment approaches.

In summary, we found several genomic markers and pathways that provide insight into biological mechanisms affecting response to CPI therapy. The analyses identified novel targets and biomarkers that have the potential to provide candidates for combination therapies or patient enrichment strategies, which could increase response rates to CPI therapy in patients with NSCLC.

Our results establish the role of FGFR signalling in the genesis of UL.

Our findings suggest that PDAs are clinically and genetically heterogeneous diseases. Understanding the heterogeneity of PDA is critically important in determining its biological potential and facilitating optimal patient management.

Importantly, these antibodies demonstrate efficacy in vivo, synergy with FGFR inhibitors, and activity against FGFR2 fusions harboring kinase domain mutations. Thus, biparatopic antibodies may serve as an innovative treatment option for patients with FGFR2-altered cholangiocarcinoma.

Administration of gemcitabine + cisplatin and gemcitabine + S-1 was discontinued due to allergic reactions. Erdafitinib was then administered; however, the disease progressed...No established treatment options for PSCCL are currently available. Identifying cancer-related genetic abnormalities may help in making treatment decisions.

These results demonstrated that laparoscopic surgical approaches are effective and frequently the first surgical approach chosen for the treatment of ACUM, but that techniques to treat these conditions are not standardized. This case is the first to demonstrate mutations in ACUM, suggesting a potential role for cancer-associated somatic mutations in their genesis. Future developments in this area may include sending more of these samples for genetic analysis, improving our understanding of how these lesions are formed, while also working to standardize how they are removed.

P2, N=316, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Mar 2025 --> Dec 2025

55% (42/77) of liquid samples with a KIT-driver mutation had a co-occurring imatinib-resistant alteration; a minority of cases harbored non-KIT mechanisms of resistance such as FGFR2 fusion, BRAF or EGFR alterations...In conclusion, known driver and TKI-resistant mutations were identified in liquid biopsies of GIST patients with high concordance to tissue in the presence of elevated TF. Liquid biopsy may be valuable in the molecular classification and medical management of GIST.

Conversely, when resistant clone cells were cultured under conditions that excluded AZD4547, the ecDNA status became similar to that of the original clone cells, and the inhibitory effect on cell growth was restored. Implications: Our results show that dynamic quantitative and qualitative changes in ecDNA can drive the intratumoural genetic heterogeneity of RTKs and resistance to RTK inhibitors.

iCCAs with pathogenic FGFR2 fusions/rearrangements and IDH1 mutations have distinct immunophenotypes. Tailoring immunotherapeutic approaches to specific molecular subsets could improve treatment outcomes across the divergent molecularly defined iCCA subtypes.

The consensus also explores the significance of emerging biomarkers, such as tumor mutation burden and microsatellite instability, in predicting responses to immune checkpoint inhibitors. The recommendations aim to enhance precision medicine approaches, improve patient outcomes, and foster the integration of molecular diagnostics into routine clinical practice.

Two phase 3 trials are currently evaluating the intravesical device system (TAR210) in FGFR-altered intermediate NMIBC (MoonRISe-1) and infigratinib in the adjuvant setting of high-risk of recurrence patients with MIBC or UTUC (PROOF-302)...Nine phase 1b/2 trials are focusing on the combination of FGFR inhibitors with ICIs, chemotherapy, or enfortumab vedotin...However, no phase 3 trial is terminated, so there is currently no level 1 evidence with long-term outcomes to support the combination of FGFR inhibitors with ICIs, chemotherapy, or targeted therapies. A better understanding of the different mechanisms of action to inhibit FGFR signaling pathways, optimal patient selection and treatment approaches is still needed.

Patterns of genetic discrepancies between primary and metastatic TC vary, offering valuable insights for clinical practice.

This study revealed that one in eight a/m UC patients had FGFR2/3 GAs, and a few changes were observed in FGFR GA status before and after treatment. Genetic testing will be beneficial for the selection of appropriate treatments after a diagnosis of a/m UC.

Only one (3.6 %) patient discontinued study treatment due to an adverse event. Futibatinib demonstrated modest antitumor activity with a safety profile consistent with previous reports in patients with gastric or GEJ cancer harboring FGFR2 amplifications, potentially warranting further investigation.

Additionally, BW710 also displayed reasonable pharmacokinetic properties with an oral bioavailability of 29 % in mice. Taken together, this study provides a potent, selective and orally bioavailable FGFR2 inhibitor for further development of FGFR2-targeted therapeutic agents.

As first-line systemic therapy, the addition of an immune checkpoint inhibitor, such as durvalumab or pembrolizumab, to gemcitabine plus cisplatin has been shown to prolong overall survival compared with gemcitabine plus cisplatin...Regarding second-line treatment after a gemcitabine-based regimen, fluorouracil and folinic acid plus oxaliplatin have been the standard regimen. Additionally, FGFR2 fusion gene/rearrangement, mutations of IDH1/2, KRAS, and BRAF, and overexpression of HER2 are promising therapeutic targets for which the effectiveness of each targeted therapy has been reported, at this time, as a second-line or later treatment.

P=N/A, N=3026, Active, not recruiting, University Health Network, Toronto | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

P2, N=120, Recruiting, Taiho Oncology, Inc. | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Dec 2026