FGFR2 (Fibroblast growth factor receptor 2)

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

P1, N=10, Recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Guangzhou Celling Biological Technology Co., Ltd.

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

Variants in FGFR signaling pathway-related factors were significantly associated with capecitabine-induced HFS.

MD simulations validated the stability and compactness of protein-ligand complexes, with principal component analysis (PCA) and free energy landscape analyses confirming these interactions' conformational stability and thermodynamic favorability. These findings suggest that uralenol, glycyrol, and abyssinone II are potential FGFR2 inhibitors and need further experimental validation for potential therapeutic use in cancer treatment.

Case studies of borderline variants (A628T, E608K, L618F) demonstrate the framework's ability to provide structurally coherent mechanistic explanations. DyVarMap bridges the gap between static structure prediction and dynamics-aware functional assessment, generating testable hypotheses for experimental validation and demonstrating the value of incorporating conformational dynamics into variant effect prediction for precision oncology.

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

P2, N=30, Not yet recruiting, Elevar Therapeutics

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.

The tumours were advanced stage at diagnosis: stage IIB (1 case), IIIC1 (2 cases), and IVB (2 cases). Our findings suggest that cervical adenosquamous carcinoma should be classified into HPV-associated and HPV-independent types and this should be reflected in updated WHO Classifications.

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.