FGFR2 mutation

Functionally, KNT-0919 selectively suppressed the proliferation of FGFR2-dependent cancer cell lines, dose-dependently inhibited FGFR2 downstream signaling, and induced apoptosis in an FGFR2-dependent manner. Moreover, KNT-0919 demonstrated favorable oral bioavailability (56%) in rats and achieved significant tumor growth inhibition in an SNU-16 gastric cancer xenograft model.

Pemigatinib (approved in 2021) demonstrated a response rate of 35.5%, futibatinib (approved in 2023) showed a response rate of 42%, and tasurgratinib (approved in 2024) achieved a response rate of 30.2%. Polyclonal on-target resistance to pan-FGFR inhibitors and increasing of FGFR2 kinase domain resistance mutations based on treatment history has been reported. Novel therapeutics, such as highly selective FGFR2 inhibitors and next-generation inhibitors, are developed and are expected to improve prognosis for patients with FGFR2 fusion-positive solid tumors.

In this secondary analysis of the BLC2001 and THOR trials, higher CTCAE hyperphosphatemia grades were associated with improved OS, PFS, and ORR. These findings suggest that hyperphosphatemia may serve as a potential biomarker of erdafitinib activity, and warrant prospective validation.

Across both diseases, circulating tumor DNA is emerging as a promising tool for prognostication, minimal residual disease assessment, response monitoring, and early resistance detection. Contemporary care increasingly depends on early molecular profiling, individualized treatment sequencing, and integration of targeted therapies, biomarker-guided immunotherapy, and clinical trials.

TP53 mutations were associated with poor prognosis and may predict greater benefit from ICI, supporting biomarker-driven stratification.

This review has made an attempt to provide a clear understanding of the genetic characteristics of iCCA, which can lead to the development of tailored treatment strategies. This has the potential to improve outcomes for patients with this challenging condition.

Liquid biopsy provides a powerful, minimally invasive tool for early detection, MRD assessment, and real-time disease monitoring in HPB cancers. Despite promising results, broader clinical adoption is limited by assay variability and the need for standardization and prospective validation. Continued innovation and large-scale studies may establish liquid biopsy as a transformative tool for early detection and personalized management of HPB cancers.

Genomic profiling reveals targetable alterations-IDH1/2 mutations, FGFR2 fusions, HER2 aberrations, BRAF V600E-driving the clinical success of specific inhibitors (ivosidenib, FGFR inhibitors, HER2-targeted ADCs/antibodies, dabrafenib/trametinib). However, overcoming tumor heterogeneity, resistance mechanisms, and optimizing combination strategies remain critical challenges. This paradigm shift towards molecularly guided therapies offers significant hope for improving BTC patient survival.

Integrated genomic and transcriptomic profiling refines prognostic stratification in cholangiocarcinoma independent of therapeutic actionability. KRAS-TP53 co-mutation and the Mesenchymal transcriptomic subtype represent independent high-risk markers detectable on routine FFPE tissue. These features complement actionable alterations and may inform patient selection and clinical trial design.

We conclude that Apert syndrome is not, in many affected individuals, associated either with substantial shortening of lifespan, or with a high risk of developing particular types of cancer. Explanation of the lack of strong cancer predisposition, despite the oncogenic nature of the FGFR2 mutations, may lie in the different signalling relationship that a mutant cell has with its neighbours when the mutation is present constitutionally, compared to occurrence as a somatic change.

One oncocytic case showed HRAS and AKT1 activating mutations; the other basaloid case had a FGFR2::SORB3 fusion. Spatial transcriptomics revealed divergent intra- and inter-tumoral signatures emphasizing the transcriptomic heterogeneity within biphasic components.

Notably, 50.8% of cases exhibited concurrent FGFR2 amplification and overexpression, and all cases with FGFR2 gene deletion also demonstrated FGFR2 overexpression. These findings suggest that FGFR2 gene amplification and deletion may contribute to FGFR2 overexpression and play a significant role in the molecular pathogenesis of mandibular AM.