FGFR2 fusion

Molecular testing has become an essential component of modern iCCA management. Broad, early, and technically integrated molecular profiling-ideally performed at initial diagnosis and interpreted in an interdisciplinary (molecular) tumor board-is critical to fully realize the potential of precision oncology in BTC.

P3, N=138, Not yet recruiting, TransThera Sciences (Nanjing), Inc.

Our findings establish FGFR2::SHTN1 as a potent oncogenic driver in various cancers, particularly in cholangiocarcinoma, highlighting a unique mechanism of constitutive activation mediated by Shootin1's CCD-II domain. This study represents the first molecular characterization of the FGFR2::SHTN1 fusion, advances understanding of FGFR2 fusion biology, and identifies a particular target for future diagnostic and therapeutic strategies in relevant malignancies.

Sex, follicular nodular disease, and Graves' disease were not significant predictors. Our findings suggest an association between fusion-driven thyroid neoplasia and florid CLT, warranting further investigation.

P2/3, N=235, Recruiting, Hutchmed | Phase classification: P2 --> P2/3 | N=128 --> 235 | Trial completion date: Dec 2025 --> Feb 2030 | Trial primary completion date: Jun 2025 --> Jun 2028

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.

Despite a broader availability of EMP in advanced CCA, patient access to targeted treatments remains suboptimal. Our results demonstrate that such treatments can dramatically impact on OS, Therefore, strategies aiming at increasing the access to (and accelerate the availability of) targeted treatments are warranted.

NGS represents the most suitable approach in molecular profiling of FGFR aberrant transcripts. Rings trial based on artificial reference samples play a pivotal role in optimizing routine diagnostic procedures filling the gap in clinical stratification of iCCA patients.

We report a novel FGFR2::TXLNB fusion in a child with hippocampal PLNTY. This fusion likely drives tumorigenesis via homodimerization and activation of MAPK/PI3K pathways, expanding PLNTY's molecular spectrum and suggesting a potential therapeutic target.

However, it also reinforces the need for careful patient selection to avoid unnecessary surgical morbidity when the anticipated oncological benefit is limited. Overall, these findings emphasize the need for prospective, age-stratified studies to better define prognostic models and guide personalized therapeutic approaches for this distinct patient population.

Evaluated on a comprehensive dataset curated from DrugBank, DuoKinaseNet achieves state-of-the-art performance, particularly on the challenging "unseen protein" benchmark, with an AUC-ROC of 0.903 for HER2 and 0.895 for FGFR2b. It significantly outperforms a wide range of baseline models, including 3D-aware methods and single-task variants, empirically validating the synergistic benefits of the dual-task learning and SPSE frameworks.

Key challenges include overcoming resistance, refining patient selection, and defining the role of FGFR inhibition in combination strategies and earlier-line or perioperative settings. Further evidence is needed to clarify long-term clinical benefit in FGFR2-altered CCA.