FGFR2 mutation

P=N/A, N=55, Not yet recruiting, Fuzhou University Affiliated Provincial Hospital; Fuzhou University Affiliated Provincial Hospital

These results highlight the importance of evaluating BDTT in SDT, as it may be the main route of hilar extension in aggressive cases.

Comprehensive genomic profiling (CGP) identified FGFR2-TACC2 fusion, TP53 mutation, and Rb1 loss. These findings suggest that targeted therapy may be considered in such rare and aggressive variants.

P3, N=480, Recruiting, J-Pharma Co., Ltd. | Not yet recruiting --> Recruiting

Lirafugratinib retains activity against multiple mutations that confer clinical resistance to pan-FGFR inhibitors. However, diverse resistance mechanisms, including various kinase domain mutations and RTK-MAPK bypass alterations, remain challenges in the treatment of FGFR2-altered tumors, even with selective FGFR2 kinase inhibition.

Pharmacologically, dedicated inhibitors like Infigratinib have demonstrated anti-tumor activity in clinical Phase II trials for FGFR-altered recurrent gliomas, while the multi-kinase inhibitor Regorafenib has shown a modest survival benefit in recurrent GBM; however, mechanistic studies indicate that effective response often relies on co-targeting bypass pathways (e.g., CLK2) and mitigating the tumor's metabolic dependency. Crucially, limited drug exposure through the blood-brain barrier (BBB) continues to be the foremost challenge, dictating optimization efforts toward compounds with favorable pharmacokinetic properties and novel delivery platforms, such as the covalent inhibitor futibatinib and liposomal formulations, to enhance brain penetrance. In conclusion, the evolving molecular landscape validates FGFR alterations as a targetable niche in gliomas, and future success depends critically on integrating comprehensive next-generation sequencing to identify aggressive FGFR variants, developing next-generation inhibitors with superior BBB permeability, and implementing rational combination strategies to achieve durable clinical benefit.

Subsequent administration of the irreversible FGFR1-4 inhibitor futibatinib was associated with a declining trend in tumor biomarkers, indicating preliminary antitumor activity against the resistant clone. This case underscores the clinical activity of FGFR inhibition in FGFR2-altered SGC and exemplifies the emergence of kinase domain mutations as a principal resistance pathway. It further suggests that irreversible FGFR inhibitors may represent a rational therapeutic strategy upon progression on prior FGFR-directed therapy, warranting further clinical investigation in this molecularly defined patient subset.

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.

Initial chemotherapy combined with immune checkpoint inhibitors achieved short-term stability, but the disease eventually progressed. Genetic testing revealed an Fibroblast growth factor receptor 2 (FGFR2) mutation, leading to a switch to targeted therapy with lenvatinib combined with capecitabine, demonstrating the value of targeted therapy in the management of rare, refractory sebaceous carcinoma.

In molecular level, PLNTY exhibits alterations in the MAPK pathway; while its DNA methylation profile demonstrates diversity. Most patients achieved seizure-free outcomes postoperatively, indicating a favorable prognosis.

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.