FGFR2 (Fibroblast growth factor receptor 2)

In summary, our study establishes the comprehensive molecular atlas and a targeted therapeutic subtyping framework, revealing therapeutic vulnerabilities and providing novel insights for advancing precision oncology in OCCC management.

Integrated genomic and transcriptomic profiling refines prognostic stratification in cholangiocarcinoma independent of therapeutic actionability. KRAS-TP53 co-mutation and the Mesenchymal transcriptomic subtype represent independent high-risk markers detectable on routine FFPE tissue. These features complement actionable alterations and may inform patient selection and clinical trial design.

Pemigatinib plus paclitaxel demonstrated antitumor activity with an acceptable safety profile in FGFR2-amplified gastric cancer. Further investigation is warranted to elucidate resistance mechanisms and validate these findings in larger cohorts.

We conclude that Apert syndrome is not, in many affected individuals, associated either with substantial shortening of lifespan, or with a high risk of developing particular types of cancer. Explanation of the lack of strong cancer predisposition, despite the oncogenic nature of the FGFR2 mutations, may lie in the different signalling relationship that a mutant cell has with its neighbours when the mutation is present constitutionally, compared to occurrence as a somatic change.

The most common baseline regimen was gemcitabine + cisplatin (34.4%). Treatment patterns, adherence, OS, HCRU, and costs demonstrated consistent trends across racial subgroups. Real-world pemigatinib treatment patterns and survival outcomes were consistent with findings from clinical trials and support continued use of pemigatinib across diverse patient groups as a key second-line treatment for CCA.

One oncocytic case showed HRAS and AKT1 activating mutations; the other basaloid case had a FGFR2::SORB3 fusion. Spatial transcriptomics revealed divergent intra- and inter-tumoral signatures emphasizing the transcriptomic heterogeneity within biphasic components.

Enfortumab vedotin plus pembrolizumab established the new first-line standard for metastatic UC, achieving a median overall survival of 33.8 months versus 15.9 months (hazard ratio [HR] 0.51, 95% confidence interval 0.43-0.61)...Critically, the IMvigor011 trial has now provided Level 1b evidence that ctDNA-guided adjuvant atezolizumab improves both disease-free survival (DFS) (HR 0.64, p = 0.0047) and OS (HR 0.59, p = 0.0131) in ctDNA(+) patients, while validating treatment de-escalation in ctDNA(-) patients (1-year DFS 95%). Erdafitinib in patients harboring FGFR2/3 alterations (HR 0.64) confirms the value of genomic profiling...In conclusion, dynamic precision oncology has transformed UC management, with the IMvigor011 trial establishing ctDNA-guided MRD status as the first phase 3-validated predictive biomarker framework for adjuvant therapy selection in a solid tumor. Implementation requires adherence to established standardization frameworks, cross-platform and cross-agent validations, and tiered implementation strategies to ensure equitable access across diverse resource settings.

Notably, 50.8% of cases exhibited concurrent FGFR2 amplification and overexpression, and all cases with FGFR2 gene deletion also demonstrated FGFR2 overexpression. These findings suggest that FGFR2 gene amplification and deletion may contribute to FGFR2 overexpression and play a significant role in the molecular pathogenesis of mandibular AM.

This study elucidates alterations in adhesion molecule expression in melanoma cells acquiring resistance to dacarbazine (DTIC) and entering the G0 state...These findings suggest that PLXNA2 down-regulation in DTIC-treated cancer cells promotes their apoptosis. Therefore, targeting focal adhesion molecules during chemotherapy can increase the sensitivity of tumor cells to anticancer treatment.

We validated ATP2B1 as a novel prognostic biomarker and developed a 160-gene classifier for subtype prediction. The C3 subtype's exceptional ICB response, independent of conventional biomarkers (PD-L1/microsatellite instability/tumor mutational burden), highlights the clinical utility of this classification system in guiding precision immunotherapy for CCA.

In vitro, recombinant FGF7 increased AKT phosphorylation and enhanced CAF contractile activation, whereas FGF7 neutralization or FGFR2 inhibition reduced AKT phosphorylation and contractility. Integrative single-cell, spatial, and functional analyses implicate an FGF7-FGFR2-PI3K/AKT axis in maintaining the contractile activation of CAFs in ovarian cancer, providing a rationale for targeting CAF signaling and ECM remodeling.

Systemic chemotherapy with gemcitabine plus cisplatin has remained the standard first-line treatment for more than a decade because most patients are diagnosed at an advanced or unresectable stage, but the associated survival benefit is limited. Accordingly, optimizing patient selection by integrating molecular and immunologic characteristics has become a critical objective for improving clinical outcomes. This review provides an overview of the recent progress in immunotherapy and targeted therapy for BTC, focusing on pivotal clinical trials, therapeutic efficacy, current limitations, and future perspectives for personalized treatment strategies.