FGFR4 overexpression

Furthermore, medical reports indicated higher rates of recurrence and bleeding intensity among smokers. These findings emphasize the potential role of FGFR3 as a key molecular factor in JNA, particularly in the context of smoking.

Moreover, we provide evidence that the combination of futibatinib with currently used chemotherapies such as irinotecan and vincristine has a synergistic effect against RMS in vitro. Moreover, limited efficacy is only observed in a PAX3-FOXO1 fusion-negative (FN) RMS cell line with mutationally activated FGFR4, whereas little or no efficacy is observed in PAX3-FOXO1 fusion-positive (FP) RMS cell lines with FGFR4 overexpression. Alternative treatment modalities such as combining futibatinib with other kinase inhibitors or targeting FGFR4 with CAR T cells or antibody-drug conjugate may be more effective than the approaches tested in this study.

The IC50 of futibatinib was ~500 nM for RMS559 and ~10 μM for RH4. Western blot showed that futibatinib inhibited FGFR4 phosphorylation in a dose dependent manner. The kinome activity assay found that futibatinib treatment resulted in SFK, AKT, and IGF1R activation.

We reported the largest single-center multiomics HER2-low BC cohort in East Asian hitherto, and revealed its molecular nature, internal heterogeneity and ethnic difference. Compared with HR- positive diseases, HER2-low BCs in the HR-negative subgroup were more likely to be a molecularly distinct entity from HER2-0 tumors. Furthermore, HR-negative HER2-low BC also accommodates higher internal heterogeneity, which was ethnicity-specific in our East Asian cohort and may infer a different treatment response.

When combined with an FGFR4 inhibitor, the anti-tumor effect of anti-PD-1 treatment increased significantly in a GC xenograft mouse model with overexpressed FGFR4. FGFRs has critical function in GC and associated with immune cell infiltration, which might be a potential prognosis biomarker and predictor of response to immunotherapy in GC.

Accordingly, FGFR4 blockade profoundly sensitized FGFR4-overexpressing GBM models towards integrin/focal adhesion kinase inhibitors. Collectively, FGFR4 overexpression contributes to the malignant phenotype of a highly aggressive GBM subgroup and is associated with integrin-related therapeutic vulnerabilities.

This work highlights how patient-derived models of human breast cancer provide powerful platforms for therapeutic target identification and analysis of drug action, and also the potential of specific FGFRs, including FGFR4, as targets for precision treatment.

We found that Src is essential for the endosomal delivery of the FGFR4 signaling complex in HCC. Our findings provide a scientific rationale for repurposing Src inhibitors for the treatment of HCCs in which the FGFR4 pathway is activated.