FGFR mutation

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.

The article provides an overview of genetic alterations that are targetable with current oncological therapies, including FDA-approved inhibitors for FGFR2 (pemigatinib, futibatinib) and IDH1 (ivosidenib), along with inhibitors targeting BRAF, HER2, NTRK, and immunotherapies for MSI-high and TMB-high tumors. Intrahepatic CCA presents a broader spectrum of therapeutic targets, including rare fusions (ALK, RET), compared to perihilar and extrahepatic CCA, which share a poor prognosis and limited therapeutic options with pancreatic cancer. In this regard, intrahepatic CCA may become the "non-small cell lung cancer of gastrointestinal oncology."

Safety was consistent with the overall FIGHT-207 population. Pemigatinib had antitumor activity and a manageable safety profile in patients with CNS tumors.

The final diagnosis was pDLGG with alterations in the MAPK pathway. The present case underscores the importance of molecular and histological features in the diagnosis of pDLGG, especially when clinical and imaging characteristics are atypical, as molecular diagnostics provide key insights for disease classification.

While FGFR alterations are rare in glioma, patients with FGFR-altered GBM may have prolonged survival, which has implications for clinical trial design. We found loss of FGFR alteration at the time of subsequent surgery, raising concern for the therapeutic potential of FGFR-targeting agents in recurrent gliomas.

P2, N=316, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2025 --> Oct 2026