FGFR2 (Fibroblast growth factor receptor 2)

This review provides a comprehensive overview of the evolving therapeutic landscape of GEC. It emphasizes the growing role of precision medicine and the integration of emerging clinical data into practice.

Pooled positive selection screens identified 474 activating and 738 mutations mediating resistance to the FGFR inhibitors pemigatinib and futibatinib, together revealing 301 druggable FGFR mutations analogous to a strong PS3/BS3 evidence level. The functional screens identified 97% of acquired resistance mutations in clinical trials. Our comprehensive catalog of every druggable mutation in the FGFR kinase domains is readily available for clinical decision support.

Furthermore, the tamoxifen-inducible loss of FGFR1/2 signaling during adulthood also impaired LTP. In addition, the conditional ablation of either FGFR1 or FGFR2 individually in the OL-lineage cells impaired LTP during adulthood, although at different levels. Thus, these observations bring up the possibility that FGFR1/2 signaling in OL-lineage cells may play a potentially novel, previously unrecognized role in OL-neuron communication for the maintenance of synaptic plasticity and memory functions in the normal adult/aging brain.

in order to capture intratumoral heterogeneity and evolving molecular events. Further investigation of FGFR2 fusion biology and combinatorial therapeutic strategies is warranted to address the clinical challenge of biomarker overlap and treatment resistance in GEA.

These findings suggest that tinengotinib might have activity in patients with cholangiocarcinoma with FGFR2 fusions that progressed following FGFR inhibitor therapy. Anti-tumour activity was also observed in patients with other FGFR alterations. The data from this phase 2 study supported the initiation of a phase 3 registration trial.

Exploratory analysis indicates that responders show significantly higher tumor PD-L1 expression than non-responders do, with median tumor proportion scores of 8% and 2%, respectively. The study is registered at ClinicalTrials.gov (NCT05236699).

Immune profiling shows P2 as immunosuppressive, characterized by LGALS9 and M2 macrophages. Our proteogenomic analyses provide a molecular landscape of LMS, revealing biological insights, patient outcome stratification, and therapeutic targets.

Some known tumor-related genes, such as FGD6, FGFR2 and FZD1, were strongly related to TIAM2 gene. TIAM2 overexpression closely correlated with tumor multiplicity and poor prognosis in resected HCC, thus being a potential therapeutic target.

Co-occurrence of GNAQ, GNAS, and IDH1 mutations may represent a molecular signature of recurrence. Further validation in larger cohorts is needed to define optimal gene panels and VAF thresholds for clinical use.

Inhibition of the RAD51B-EZH2 axis allows the re-expression of functional ERα, making TNBC targetable by endocrine therapy. Consistently, the combination of EZH2 inhibitor with tamoxifen effectively reduces TNBC progression, suggesting that the RAD51B-EZH2 axis is a potential therapeutic target for TNBC.

Our findings suggest that GBM-derived 3D neurosphere cultures exhibit HIF-1α-regulated molecular features consistent with CSC and a potential mimicry of chemoresistance-associated traits rather than a direct demonstration of chemoresistance. These correlative observations support a potential link between metabolic reprogramming and the emergence of such phenotypes in response to hypoxic stress. Further investigation is needed to establish causal relationships and to better understand the underlying mechanisms.

Combined inhibition of FGFR1 and MET significantly suppressed tumor growth in resistant cells. These findings establish MET amplification and GAB1-SHP2 signaling as central mediators of erdafitinib resistance in FGFR1-amplified MIBC and support dual FGFR1/MET targeting as a promising therapeutic strategy.