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PubMed2026

C-Terminal Truncation and Fusion Partner Determine Oncogenicity of FGFR3.

UNLABELLED: Genomic alterations affecting components of the fibroblast growth factor (FGF) signaling axis can trigger aberrant pathway activation and tumor development. Genomic truncation of the FGF receptor 2 (FGFR2) exon 18 (E18) disrupts the FGFR2 carboxy (C)-terminal tail, acting as a potent driver alteration across multiple tumor types. In this study, we analyzed human oncogenomic datasets to reveal that E18 truncations are similarly prevalent in FGFR3, an FGFR2 paralog. FGFR3 E18 truncations primarily occur due to rearrangements (RE) that involve transforming acidic coiled-coil-containing protein 3 (TACC3), resulting in FGFR3ΔE18-TACC3 gene fusions. In contrast to E18-truncated FGFR2, functional in vitro and in vivo examination of Fgfr3 variants demonstrated that the truncation of Fgfr3 E18 is insufficient to promote oncogenic activity in cell lines or in the lungs and mammary glands of mice. Only the combination of an Fgfr3 E18 truncation with a RE partner gene that encodes a receptor-dimerizing domain resulted in the development of tumors, which were sensitive to FGFR inhibition. Overall, these findings suggest that patients with cancers that are positive for rearranged FGFR3, resulting in E18 truncation and a fusion to dimerizing partners, should be considered for FGFR-targeted therapies. SIGNIFICANCE: FGFR3, unlike its paralog FGFR2, requires both a C-terminal truncation and fusion to a partner gene that retains the expression of a dimerizing domain to effectively drive oncogenic signaling and tumorigenesis.

Receptor, Fibroblast Growth Factor, Type 3↗

PubMed2026

SDC1+ CAFs secreting CTGF drive tumour metastasis via FGFR3 signalling in cancers.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are key stromal components of the tumour microenvironment (TME) that profoundly influence tumour progression. However, CAFs exhibit pronounced phenotypic and functional heterogeneity, and whether conserved CAF subtypes with shared functional hallmarks exist across different cancer types remains unclear. OBJECTIVE: We sought to uncover universal CAF subtypes that transcend tumour origins, defining their core molecular signatures and pro-tumorigenic functions within the TME. DESIGN: We constructed a pan-cancer CAF atlas through single-cell transcriptomic analysis of 554 specimens across 14 cancer types. To validate the findings, we performed further functional analyses, including in vitro migration and invasion assays, in vivo lymphatic metastasis models and mechanistic studies focusing on candidate signalling pathways. RESULTS: We identified a conserved syndecan 1 (SDC1) + CAF subset associated with advanced tumour stage and poor outcomes. These CAFs enhanced tumour cell migration and invasion in vitro and promoted lymphatic metastasis in vivo. This effect is mediated through connective tissue growth factor (CTGF) secretion, which activates fibroblast growth factor receptor 3 (FGFR3) signalling in tumour cells to induce epithelial-mesenchymal transition (EMT). Blocking CTGF or FGFR3 signalling abrogated these effects. We also found that kruppel like factor 6 (KLF6) directly regulates CTGF in SDC1+ CAFs, establishing a complete KLF6-CTGF-FGFR3 metastatic axis. CONCLUSIONS: Our study establishes SDC1+ CAFs as a universal, metastasis-promoting CAF subset across multiple cancer types and uncovers a novel KLF6-CTGF-FGFR3 axis that drives EMT and tumour dissemination. These findings provide mechanistic insight into CAF-tumour cell crosstalk and highlight actionable stromal targets for anti-metastatic therapies across diverse malignancies.

Humans↗

PubMed2026

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗

PubMed2024

Dual diagnosis of achondroplasia and mandibulofacial dysostosis with microcephaly.

BACKGROUND: Achondroplasia and mandibulofacial dysostosis with microcephaly (MFDM) are rare monogenic, dominant disorders, caused by gain-of-function fibroblast growth factor receptor 3 (FGFR3) gene variants and loss-of-function elongation factor Tu GTP binding domain-containing 2 (EFTUD2) gene variants, respectively. The coexistence of two distinct Mendelian disorders in a single individual is uncommon and challenges the traditional paradigm of a single genetic disorder explaining a patient's symptoms, opening new avenues for diagnosis and management. CASE PRESENTATION: We present a case of a female patient initially diagnosed with achondroplasia due to a maternally inherited pathogenic FGFR3 variant. She was referred to our genetic department due to her unusually small head circumference and short stature, which were both significantly below the expected range for achondroplasia. Additional features included distinctive facial characteristics, significant speech delay, conductive hearing loss, and epilepsy. Given the complexity of her phenotype, she was recruited to the DDD (Deciphering Developmental Disorders) study and the 100,000 Genomes project for further investigation. Subsequent identification of a complex EFTUD2 intragenic rearrangement confirmed an additional diagnosis of mandibulofacial dysostosis with microcephaly (MFDM). CONCLUSION: This report presents the first case of a dual molecular diagnosis of achondroplasia and mandibulofacial dysostosis with microcephaly in the same patient. This case underscores the complexity of genetic diagnoses and the potential for coexistence of multiple genetic syndromes in a single patient. This case expands our understanding of the molecular basis of dual Mendelian disorders and highlights the importance of considering the possibility of dual molecular diagnoses in patients with phenotypic features that are not fully accounted for by their primary diagnosis.

Humans↗

PubMed2026

Lynch syndrome-associated urothelial carcinoma: clinical and molecular findings from a single-institution cohort.

Lynch syndrome-associated urothelial carcinoma (LS-UC) is a rare and undercharacterized clinical entity. While FGFR3 alterations are well described in sporadic urothelial carcinoma, their prevalence and clinical implications in LS-UC remain unclear. We aimed to provide a comprehensive clinical and molecular characterization of LS-UC. We conducted a retrospective single-center study including patients with Lynch syndrome (LS) and histologically confirmed urothelial carcinoma (UC). Clinical, pathological, treatment, and follow-up data were collected. Targeted next-generation sequencing was performed on available tumor samples to assess genomic alterations, with particular attention to FGFR3 mutations. A total of 27 patients with LS-UC were identified, with a predominance of upper urinary tract involvement (70%). Most tumors were diagnosed at an early stage and initially managed with local treatment. During a median follow-up of 92 months, 48% of patients experienced recurrence, with a median time to recurrence of 37 months. Recurrences were predominantly local and were mainly managed with additional surgical or intravesical treatments. No deaths were attributable to UC at last follow-up. Molecular analysis was feasible in 9 cases. FGFR3 mutations were detected in 67% of evaluable samples, with the recurrent p.Arg248Cys hotspot identified in 55% of cases. Additional alterations involved TP53, SWI/SNF complex genes, and PIK3CA, which co-occurred with FGFR3 p.Arg248Cys. No gene fusions were identified. This study expands the limited molecular and clinical evidence on Lynch syndrome-associated urothelial carcinoma. Beyond confirming the recurrent role of FGFR3 (notably p.Arg248Cys), our comprehensive multigene profiling enriches the current genomic knowledge for this rare population. Multi-center collaborative efforts remain essential to aggregate larger datasets and ultimately guide personalized patient management.

Humans↗

PubMed2026

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans↗

PubMed2025

Genomic subtypes of non-muscle-invasive bladder cancer: guiding immunotherapy decision-making for patients exposed to aristolochic acid.

BACKGROUND: The limited genomic data on non-muscle-invasive bladder cancer (NMIBC) hampers our understanding of its carcinogenesis and development. Specifically, Aristolochic acid (AA), a potent human carcinogenic compound from aristolochia plants and commonly found in Chinese herbal medicine, has been extensively documented as being closely associated with the onset and progression of bladder cancer. However, the field of AA-induced NMIBC remains largely unexplored in terms of its genomic and molecular characteristics, as well as clinical therapeutic strategies. METHODS: To bridge this knowledge gap, we conducted a comprehensive study using a cohort of 81 NMIBC samples. We performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) to obtain detailed genomic and transcriptomic data. We subjected these datasets to genomic analysis and subtype analysis to gain valuable insights into NMIBC. RESULTS: By temporally dissecting mutations in NMIBC specimens, we identified a comprehensive mutational landscape of NMIBC and the associations of these mutations with recurrence-free survival. Additionally, we discerned four genomic subtypes of NMIBC: AA-like, FGFR3/HRAS, FGFR3 & chr9Del, and genome instability (GI). The AA-like subtype presented a high frequency of gene mutations along with a pronounced AA mutagenesis signature of SBS22 (Fisher test: P-value 3.5e-4, OR 25.25) even after temporal dissection. The FGFR3/HRAS subtype exhibited FGFR3 or HRAS mutations with few copy number alterations (CNAs). The FGFR3 & chr9Del subtype was characterized by the co-occurrence of chr9p and chr9q deletions as well as FGFR3 mutations, while the GI subtype showed a high frequency of CNAs. Notably, the AA-like and GI subtypes demonstrated better outcomes after immunotherapy, whereas the FGFR3/HRAS subtype showed poorer outcomes. CONCLUSIONS: Our findings provide novel perspectives on the genomics of NMIBC, unveiling four prominent genomic subtypes, each showing different outcomes following immunotherapy. TRIAL REGISTRATION: No. 2019PHB268-01 (retrospectively registered on February 14, 2020).

Humans↗

PubMed2025

Diffusely metastatic glioblastoma with FGFR3::TACC3 fusion: cell-free DNA fragmentation analyses and molecular characterization of matched primary and metastatic tumor sites.

Extracranial metastasis of IDH-wildtype glioblastoma is very rare and poorly understood at the molecular level. We report a case of FGFR3::TACC3 fusion IDH-wildtype glioblastoma in a 61-year-old male, whose preoperative blood sample showed highly aberrant cfDNA fragmentation patterns, which could be suggestive of early systemic dissemination, undetected by standard-of-care imaging of his body. Eleven months post-resection and adjuvant therapy, he developed widespread extracranial metastases. Comprehensive molecular profiling of matched primary and metastatic tumors revealed broadly conserved genomic, transcriptomic, and copy number landscapes, with the metastasis harboring an additional ERCC6 deletion and enriched expression of receptor tyrosine kinase signaling genes. These findings provide rare insight into the genetic continuity and evolution underlying IDH-wildtype glioblastoma metastasis.

Humans↗

PubMed2025

Detection of heterogeneous resistance mechanisms to tyrosine kinase inhibitors from cell-free DNA.

Though there has been substantial progress in the development of anti-human epidermal growth factor receptor 2 (HER2) therapies to treat HER2-positive metastatic breast cancer (MBC) within the past two decades, most patients still experience disease progression and cancer-related death. HER2-directed tyrosine kinase inhibitors can be highly effective therapies for patients with HER2-positive MBC; however, an understanding of resistance mechanisms is needed to better inform treatment approaches. We performed whole-exome sequencing on 111 patients with 73 tumor biopsies and 120 cell-free DNA samples to assess mechanisms of resistance. In 11 of 26 patients with acquired resistance, we identified alterations in previously characterized genes, such as PIK3CA and ERBB2, that could explain treatment resistance. Mutations in growing subclones identified potential mechanisms of resistance in 5 of 26 patients and included alterations in ESR1, FGFR2, and FGFR4. Additional studies are needed to assess the functional role and clinical utility of these alterations in driving resistance.

Humans↗

PubMed2025

Recurrent FGFR2 and PIK3CA Mutations in Sialoblastoma.

PURPOSE: Sialoblastoma is an extremely rare low-grade malignant salivary gland neoplasm that presents at birth or early infancy and has heterogeneous clinical behavior. Due to its rarity, the molecular landscape remains incompletely characterized. We aimed to expand the current understanding of the genetic alterations in sialoblastoma through comprehensive molecular analysis. METHODS: Five sialoblastoma cases were retrieved from four institutional archives. Clinical and pathologic review was performed, and targeted next-generation sequencing was conducted using clinically validated panels. Copy number analysis was performed on four cases. RESULTS: The cohort included five patients with tumors located in parotid gland (n = 2), minor salivary glands (n = 2), and submandibular gland (n = 1). Four patients were diagnosed before 6 months of age. Histologically, all tumors showed solid organoid nests with primitive basaloid cells, dense fibrous stroma, and mitotic activity ranging from 8 to 25 per 10 high-power fields. Recurrent FGFR2 p.C382R variants were identified in 80% (4/5) of cases. Additional alterations were seen in FGFR2 p.C382R mutated tumors, including PIK3CA hotspot mutations in two cases (p.R88Q, p.R38H) and a truncating FGFR2 variant (p.L776Rfs) in one. The single tumor that lacked FGFR2 mutations harbored a CTNNB1 p.I35T variant and showed more favorable histologic features. Copy number analysis revealed recurrent whole-chromosome gains of chromosomes 8, 10, and 11. CONCLUSION: A distinct subset of sialoblastoma has FGFR2 p.C382R hotspot mutation as the predominant driver mutation. Tumors with this mutation tend to have solid growth pattern, aggressive histologic features, and clinical behavior. The identification of concurrent genomic alterations expands the molecular landscape of this rare tumor. The detection of alternative drivers, such as CTNNB1 hotspot mutations typical of basal cell adenoma, also suggests that a subset of sialoblastoma may represent other salivary gland tumors presenting in infancy.

Humans↗

PubMed2026

A phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of vosoritide in children with hypochondroplasia: CANOPY HCH-3 study design.

BACKGROUND: Hypochondroplasia is a skeletal dysplasia characterized by disproportionate short stature that is caused by gain-of-function variants in the fibroblast growth factor receptor 3 gene (FGFR3), which negatively regulates endochondral bone growth. Current treatments are based on symptom management; there are no treatments targeting the signaling pathways that underlie hypochondroplasia. Vosoritide, a C-type natriuretic peptide analog that counteracts overactive FGFR3 signaling to stimulate endochondral bone growth, is approved for the treatment of achondroplasia in children. A phase 1/2 clinical trial demonstrated that vosoritide treatment for 1 year increased growth in children with hypochondroplasia and was well-tolerated. OBJECTIVES: The objectives of CANOPY HCH-3 are to evaluate the efficacy and safety of vosoritide for the treatment of hypochondroplasia in children. DESIGN: CANOPY HCH-3 was a phase 3, randomized, double-blind, placebo-controlled, multicenter study. METHODS AND ANALYSIS: Children aged ≥3 to <18 years with confirmed hypochondroplasia who had ≥6 months of pre-treatment standing height from a prior observational study before randomization were enrolled. Participants were randomized to receive 52 weeks of daily treatment with vosoritide or placebo, followed by 2 weeks of safety follow-up. The primary endpoint is change from baseline in annualized growth velocity at week 52 versus placebo. ETHICS: CANOPY HCH-3 was conducted in accordance with the Council for International Organizations of Medical Sciences International Ethical Guidelines, the principles of the Declaration of Helsinki and of Good Clinical Practice, and applicable laws and regulations. Protocols were approved by relevant local health authorities, ethics committees, and institutions. Written informed consent from the participant, or parent or legal guardian, was obtained prior to any study-related procedures being performed. DISCUSSION: CANOPY HCH-3 will provide further evidence for the efficacy and safety of vosoritide in children with hypochondroplasia.

clinical trial↗

PubMed2026

A Phase 3 Trial of Vosoritide in Children with Hypochondroplasia.

BACKGROUND: Hypochondroplasia, a fibroblast growth factor receptor 3 (FGFR3)-related skeletal condition characterized by disproportionate short stature and a spectrum of clinical features, has no available targeted therapies. Vosoritide, a C-type natriuretic peptide analogue approved for the treatment of achondroplasia, is being investigated for hypochondroplasia. METHODS: In this phase 3, multicenter trial, children with hypochondroplasia who were 3 to less than 18 years of age were randomly assigned to receive once-daily subcutaneous injections of vosoritide or placebo for 52 weeks per weight-band dosing regimen. The primary end point was change from baseline in annualized growth velocity at week 52 versus placebo. Confirmatory statistical testing using hierarchical procedures to control for type I error at the one-sided 0.025 significance level (equivalent to the two-sided 0.05 level) was performed for the primary and six key secondary efficacy end points. The safety and side effect profile of vosoritide versus placebo was assessed. RESULTS: A total of 81 participants were randomly assigned to receive vosoritide (n=41) or placebo (n=40). At week 52, the least squares mean (LSM) change from baseline in annualized growth velocity was 1.95 cm/year with vosoritide versus -0.39 cm/year with placebo (LSM difference of 2.33 cm/year; 95% confidence interval, 1.85-2.82 cm/year; two-sided P<0.0001). Most participants in the vosoritide group (87.8%) and the placebo group (72.5%) experienced at least one adverse event (AE). There were no reports of grade 3 or higher AEs, AEs leading to treatment discontinuation, or deaths. CONCLUSIONS: One year of vosoritide treatment significantly increased linear growth in children with hypochondroplasia. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov number, NCT06455059.).

Journal Article↗

PubMed1976

Extent of mitogen receptor occupancy and modulation of mitogen receptor exposure: possible mechanisms for the regulation of cell growth.

125I-Insulin was used as a model mitogen to examine the relationships of mitogen receptor occupancy and exposure in controlling cell replication. Labeled hormone was bound to substratum-attached, confluent fibroblasts with two affinities, K1 approximately equal to 2 X 108 M-1 and K2 approximately equal to 0.8 X 107 M-1. Approximately 9,000 receptors per cell were calculated from a scatchboard plot analysis with 80% of them of the affinity type. Treatment of confluent fibroblasts with 1.0 to 10 microng/ml of trypsin for 10 min increasd the number of exposed K2 sites by a factor of 2 to 3. Culturing the fibroblasts in the absence of serum for 12 to 24 hr also increased the quantity of exposed K2 sites to 60,000 per cell. The addition of unlabeled insulin to untreated, trypsin-treated, or serum-starved fibroblasts resulted in a stimulation of 2-deoxyglucose transport and thymidine incorporation activity that was proportional to the observed level of 125I-insulin binding. The quantity of exposed insulin receptors on uninfected fibroblasts decreases as the cell culture density increases. Hormone binding to B77 virus-transformed fibroblasts also decreases with culture density but plateaus at a density of 6 X 105 cells/plate. This resulted in a 2- to 3-fold difference in the level of exposed receptors between the uninfected and virus-transformed cells in confluent cultures, and proportionally higher rates of sugar transport and thymidine incorporation activity. Trypsin treatment and 12 hr of growth in the absence of serum did not result in an increase in the level of recepto exposure in the virus-transformed cells. The results of this study suggest that the pleotypic events associated with the stimulation of cell replication as represented by sugar transport and DNA synthesis are dependent upon and proportional to mitogen receptor occupancy. The control of cell replication, however, appears to be linked by a presently unknown mechanism with the degree of exposure of mitogen recipotrs. Receptor concentration is high and is similar in rapidly growing uninfected and virus-transformed cells, but the subsequent decrease observed with an increase in culture density reaches an early plateau for the transformed cells. This difference in exposed receptors could provide the growth advantage that is the hallmark of transformed cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2026

Efficacy and safety of infigratinib in patients with refractory advanced gastric or gastroesophageal junction adenocarcinoma harboring FGFR2 gene amplification: a single-arm, multicenter phase 2 trial.

BACKGROUND: FGFR2 has garnered attention as a promising therapeutic target for gastric cancer (GC) because of its role in GC progression. Infigratinib, an FGFR1-3 selective tyrosine kinase inhibitor, has shown potential in preclinical GC models. METHODS: Infigratinib was evaluated in a phase 2 trial for patients with FGFR2-amplified GC or gastroesophageal junction (GEJ) adenocarcinoma who had failed two or more lines of systemic treatment for locally advanced or metastatic disease. A total of 21 patients received 125 mg of infigratinib orally once daily on a "3 weeks on, 1 week off" schedule. RESULTS: Infigratinib showed preliminary antitumor activity in this molecularly selected population, as reflected by a confirmed objective response rate of 23.8% (95% CI, 8.2-47.2) with median progression-free survival of 3.4 months and median overall survival of 6.7 months. The most common grade 3-4 adverse events were elevated aspartate aminotransferase, decreased white blood cell count, and neutropenia. No treatment-related deaths occurred. Exploratory genomic analyses identified alterations in individual patients with disease progression that may be associated with resistance; however, these findings were based on a limited number of cases and should be interpreted as hypothesis-generating. CONCLUSIONS: The findings support continued investigation of FGFR-targeted strategies in FGFR2-amplified GC/GEJ adenocarcinoma, while underscoring the need for larger studies, refined biomarker selection, and deeper characterization of resistance mechanisms. TRIAL REGISTRATION: NCT05019794, Registered 28 July 2021, https://clinicaltrials.gov/study/NCT05019794 .

Humans↗