FGFR2 mutation

P1, N=160, Recruiting, SystImmune Inc. | N=120 --> 160

Fusion transcript analysis identified 91 recurrent fusions, including novel partners with ERBB2, MED1, and CDK12, suggesting the possibility of unique molecular events. Interpretation and conclusions This study demonstrates that Indian breast cancer patients exhibit molecular subtypes and actionable mutations comparable to Caucasian cohorts.

Stereotactic biopsy of diffuse brainstem tumors can be performed safely. Identification of targets for personalized therapy may be essential for management of these patients.

While approved pan-FGFR inhibitors provide clinical benefit, their durability is limited by acquired, often polyclonal, on-target resistance mutations affecting key regions of the FGFR2 kinase domain, including the gatekeeper residue (V565), molecular brake residues (N550, E566, K642), and other key variants...Given FGFR2-associated toxicities and the need for subtype selectivity, FGFR4 inhibition was prioritized as a selectivity determinant, while sparing FGFR1 was considered less critical. Guided by structure-based drug design, a reversible aminopyrimidine screening hit was optimized into a novel covalent inhibitor series active against FGFR2 wild-type and clinically relevant resistance mutations. An advanced lead 13 showed favorable potency, ADME properties, and demonstrated proof-of-concept in vivo efficacy in an FGFR2-amplified xenograft model comparable with the standard of care.

The integration of NGS and the subsequent use of matched targeted therapy significantly improved survival outcomes in selected patients with advanced BTC, highlighting the importance of precision medicine strategies.

Only one patient died 16 months after surgery due to an unrelated traffic accident.

A comprehensive literature search was performed in PubMed/MEDLINE, Embase, and Scopus for studies published from January 2000 to February 2026, using combinations of the terms 'cholangiocarcinoma,' 'FGFR2,' 'fibroblast growth factor receptor,' and 'futibatinib.' Relevant clinical trials, translational studies, and review articles were screened for inclusion. Futibatinib represents the most biologically rational FGFR inhibitor currently available for FGFR2-altered CCA, as it directly addresses the dominant mechanism limiting the efficacy of earlier agent, on-target resistance driven by secondary FGFR2 kinase domain mutations.

Pathological subtypes of CCA exhibit distinct clinical outcomes and molecular characteristics. Classification based on pathological subtype provides a useful framework for understanding the clinical and molecular heterogeneity of CCA.

Parallel translational work using cfDNA-based liquid biopsy has mapped a spectrum of secondary kinase-domain mutations that underlie acquired resistance, informing the development of next-generation FGFR2-selective inhibitors (eg, lirafugratinib) and combination strategies with EGFR/ERBB blockade. Collectively, these data underscore the need for comprehensive molecular profiling and innovative umbrella trial designs to optimise targeted therapy in this rare, biologically heterogeneous malignancy.

Retrospective data indicate that gemcitabine plus platinum-based chemotherapy achieves the most consistent efficacy among conventional regimens, with median overall survival (OS) of 10-16 months...For clinical settings where comprehensive genomic profiling is not feasible, we discuss a pragmatic surrogate-based approach using imaging characteristics and serum tumor markers to guide initial treatment selection. We also address post-progression treatment considerations, including phenotype-based regimen switching and the role of re-biopsy.

P1/2, N=490, Completed, Elevar Therapeutics | Active, not recruiting --> Completed | Trial completion date: Dec 2027 --> Sep 2025

Metastatic enrichment of CDH1 and MLH1 supports their roles in invasion and therapeutic resistance. Together, these findings highlight candidate biomarkers and actionable pathways warranting validation in larger, multi-omic cohorts to refine precision treatment strategies for this aggressive gastric cancer subtype.