FGFR2 mutation

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.

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.

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.

These age-specific molecular subtypes correlated with significant survival differences. Our study identifies conserved age-specific molecular subtypes of EC and reveals population-specific genomic features, underscoring the need for age-tailored and ethnicity-aware therapeutic strategies.

The pockets made by these regions can act as allosteric sites for inhibitor design. Overall, this study may aid in better therapeutic intervention against endometrial cancer.

Our findings provide a comprehensive genomic landscape of Korean gastric cancer and underscore the clinical relevance of integrating genomic and established biomarkers to advance precision oncology.

We predicted three small molecules targeting FGFRs, and ZINC000101867325 shows superior chemical bond types and stability with FGFR1/2/3, and inhibits FGFR signaling in CRC cell lines. This study provides novel FGFRs inhibitors, which enrich treatment strategies for cancers.

Validation using exogenous mutation expression assays confirmed the majority of predicted loss-of-function, gain-of-function, neomorphic and neutral (no predicted functional effect) mutations in PIK3CA and FGFR2. These findings may inform targeted therapy decisions for patients with mutations of unknown significance in established oncogenes.

Selective FGFR tyrosine kinase inhibitors, including the reversible inhibitor pemigatinib and the irreversible inhibitor futibatinib, have demonstrated clinically meaningful response rates and durable disease control in patients with previously treated FGFR2-altered iCCA, leading to regulatory approvals and the incorporation of FGFR inhibition into contemporary treatment paradigms. In addition, we highlight the growing role of circulating tumor DNA as a noninvasive tool for longitudinal molecular monitoring and treatment guidance. Together, these insights underscore the central role of FGFR2-directed therapy in precision oncology for biliary tract cancer and provide a framework for optimizing and extending targeted treatment in this molecularly defined disease subset.

Adding ivosidenib to gemcitabine and cisplatin in this study demonstrated a challenging safety profile in advanced CCA. Further research and dose optimization are warranted to confirm these findings and optimize the integration of targeted therapies into first-line regimens.

Standardized molecular testing strategies will be key to enable the integration of more consistent and comparable genomic datasets across studies. Further, by elucidating the prognostic relevance of individual genomic alterations, our insights carry significant implications for interpreting single-arm clinical trials within genomically stratified patient cohorts and underscore the importance of randomized studies to delineate the benefit of targeted therapies.