FGFR mutation

Innovative approaches, including the second-generation FGFR TKIs, monoclonal antibodies (mAbs), FGF traps, antibody-drug conjugates, and synergistic combinations with immunotherapy or other receptor tyrosine kinase (RTK) inhibitors, are discussed to overcome resistance. Overall, this review offers theoretical insights and proposes strategies to tackle resistance to FGFR-directed treatments in lung cancer.

Demonstrating the mutation carried by the tumor is very critical in this regard. The purpose of this article is to focus on the treatment of thalamic glioma in pediatric patients in light of molecular information.

Moreover, integrating splicing modulators with FGFR TKIs may overcome drug resistance. Understanding the intricate interplay between FGFR signaling and RNA splicing will not only advance biomarker-guided therapeutic development but also provide a novel framework to counteract tumor adaptability, ultimately improving outcomes in FGFR-driven malignancies.

The targets evaluated have potential drugs currently under trial phase. This may help to define the subgroup for use of targeted therapy in NSCLC-SCC and in designing new treatment protocols.

P1/2, N=70, Recruiting, Incyte Biosciences International Sàrl | Trial completion date: Jan 2026 --> Feb 2028 | Trial primary completion date: Jan 2026 --> Feb 2028

We propose that such a low-intensity regimen may be suitable for older patients with AML, who are unfit for intensive chemotherapy. We also present data indicating that PRI5202 induces myeloid differentiation in blasts from patients with myelodysplastic syndrome (MDS), and we propose to further investigate PRI5202 as a differentiation therapy for patients suffering from MDS.

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.

Similar haploidy is found in 3 additional high-grade astrocytoma by literature review, all harbor a single gene mutation in the MAPK pathway. We propose that the massive chromosome loss might serve as a significant mechanism contributing to the unusual malignant transformation of benign brain tumors activated by the MAPK pathway.

Loss of PRR14L prolongs SAC-dependent mitotic arrest in response to microtubule depolymerization but, paradoxically, leads to catastrophic mitotic errors upon SAC abrogation by MPS1 inhibitors. A model derived from our findings provides a rationale for exploiting MPS1 inhibition as a potential vulnerability in cancers containing either PRR14L loss of function mutations or FGFR-TACC3 fusions.

The noteworthy observation is out of 7 Triple Negative Breast Cancer patients three patients were negative for any mutation. Hence, the association of genetic variation with clinicopathological parameters will be helpful in the selection of targeted treatment.

Accordingly, they may be more appropriately classified as NSCLC, not otherwise specified (NOS), rather than strictly as ADC or SCC. Given their molecular complexity, broader genomic profiling may be warranted in these cases, even though current guidelines do not recommend routine molecular testing for SCC.

These findings establish that erdafitinib exerts off-target anti-angiogenic effects by blocking VEGFR2 phosphorylation and downstream signaling, supporting its repurposing potential for anti-VEGF-resistant retinal vascular diseases. Further studies should address its intraocular pharmacokinetics and long-term safety.