FGFR fusion

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.

Systemic treatment for advanced CCA is rapidly evolving toward biomarker-driven and immunotherapy-based strategies. Integration of molecular profiling and precision oncology may further improve individualised treatment and clinical outcomes.

Most patients followed an aggressive clinical course, including metastases and disease-related mortality. These findings expand the spectrum of sarcomas driven by FGFR gene fusions, underscoring the importance of molecular testing for accurate diagnosis and potential targeted therapy in high-grade sarcomas with myogenic features.

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.

P2/3, N=201, Recruiting, Janssen Cilag International | Active, not recruiting --> Recruiting

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

Adjuvant capecitabine has become standard postoperative care following the BILCAP trial outcome. Intended for nonresectable cases, systemic therapy with gemcitabine + cisplatin serves as first-line therapy (median OS, 11.7 months)...Future directions hinge on wider liquid biopsy adoption, especially ctDNA testing to enable earlier iCCA detection, real-time monitoring, and faster therapy adjustments against emerging resistance. Routine molecular profiling identifies FGFR fusions and IDH1 mutations to guide targeted iCCA therapies; steady funding and tumor board integration remain essential for broader access.

The PREICO project suggests the feasibility of implementing a centralized CGP prescreening program in a public healthcare setting for tumor types without public NGS access. CGP identified potentially actionable alterations in a substantial proportion of patients across tumor types, informed treatment decisions and facilitated access to clinical trials in selected cases.

During follow-up, the patient underwent a second neurosurgery, where histological evaluation indicated a GMB. This article presents clinical and radiological data, morphology, immunohistochemistry, molecular features, and treatment to enhance the clinical and pathological understanding of PLNTY with FGFR3-TACC3 fusion for all professionals involved in medical decisions.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

It covers their mechanisms in driving cancer, their potential as biomarkers to predict treatment response, and the emerging challenges and opportunities for FGFR-targeted therapy. Ultimately, a deeper understanding of FGFR rearrangements is critical for advancing precision oncology and improving patient benefit.

This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies.