FGFR2 (Fibroblast growth factor receptor 2)

We demonstrated the real-world genomic characteristics of BTC patients, which may have promising implications for the development and application of precision medicine in the future. Well-designed prospective studies are mandatory to validate the predictive role of significant genomic alterations observed in our study.

Personalized treatment recommendations were made for 13 patients, and 11 received matched therapies: dabrafenib ± trametinib (n = 9), futibatinib (n = 1), or binimetinib (n = 1). These findings demonstrate frequent actionable alterations in ameloblastoma and clinically meaningful responses of targeted therapies. Incorporating precision oncology into standard care may facilitate personalized, less morbid surgery and improved outcomes in these rare tumors.

The contemporary therapeutic landscape integrates targeted agents with immune checkpoint inhibitors; yet, optimal treatment sequencing and biomarker-driven patient selection require further refinement. This review synthesizes current evidence-based approaches and emerging therapeutic paradigms in hepatobiliary oncology, examining how molecular characterization can bridge the precision medicine gap between BTC and HCC to improve patient outcomes.

CNS involvement in ACC was associated with poor outcomes despite multimodal therapy. NOTCH1 alterations and leptomeningeal disease were frequent in this cohort, but these findings should be interpreted as hypothesis-generating given the small sample size and absence of a matched non-CNS comparator cohort.

In this study, by incorporating diverse molecular glue handles and amino acid-based degrons into the solvent-exposed exit vectors of infigratinib, we synthesized a library of 30 candidate MGDs...Mechanistic investigations revealed that the covalent engagement of the gluing handle is a critical determinant for successful proteasomal degradation of FGFR2. This work provides a framework for the rational transformation of kinase inhibitors into covalent molecular glue degraders, underscoring the potential of FGFR degradation as a next-generation precision medicine strategy for FGFR2-driven malignancies.

Functionally, KNT-0919 selectively suppressed the proliferation of FGFR2-dependent cancer cell lines, dose-dependently inhibited FGFR2 downstream signaling, and induced apoptosis in an FGFR2-dependent manner. Moreover, KNT-0919 demonstrated favorable oral bioavailability (56%) in rats and achieved significant tumor growth inhibition in an SNU-16 gastric cancer xenograft model.

Pemigatinib (approved in 2021) demonstrated a response rate of 35.5%, futibatinib (approved in 2023) showed a response rate of 42%, and tasurgratinib (approved in 2024) achieved a response rate of 30.2%. Polyclonal on-target resistance to pan-FGFR inhibitors and increasing of FGFR2 kinase domain resistance mutations based on treatment history has been reported. Novel therapeutics, such as highly selective FGFR2 inhibitors and next-generation inhibitors, are developed and are expected to improve prognosis for patients with FGFR2 fusion-positive solid tumors.

In this secondary analysis of the BLC2001 and THOR trials, higher CTCAE hyperphosphatemia grades were associated with improved OS, PFS, and ORR. These findings suggest that hyperphosphatemia may serve as a potential biomarker of erdafitinib activity, and warrant prospective validation.

EBC-based cfRNA profiling provides a feasible, non-invasive approach for molecular characterization of advanced lung adenocarcinoma. Among the genes examined, PIK3CA showed the strongest diagnostic signal, FGFR2 demonstrated prognostic significance, and EGFR showed the clearest cross-sample concordance and treatment-associated relevance. Larger independent validation studies are required before clinical implementation.

This study confirms that, despite its name, PLNTY is not limited to pediatric patients. Findings underscore the highly epileptogenic nature of PLNTY and its recognizable electroclinical features, potentially related to its distinctive neuropathology. Most PLNTYs show mitogen-activated protein kinase (MAPK) pathway activating alterations, demonstrated by BRAFV600E mutation and FGFR3 fusion.

This was the largest, first-line, randomized, phase 3 trial of a targeted therapy for advanced FGFR2-rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.

In this retrospective analysis, ctDNA represents a practical alternative to tumor tissue for NGS-based biomarker testing in aBTC, offering improved access and faster results.