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Ana Vivancos

Publications and source records attributed to Ana Vivancos.

3 recordsLinked to original sources
PubMed2026

Application of a Translational Research Platform to Unveil Efficacy Signals and Mechanisms of Resistance of FGFR Inhibitors in Multiple FGFR-Altered Solid Tumors.

PURPOSE: The predictive value of fibroblast growth factor receptor (FGFR) amplifications (amp) and the role of FGFR mutations (mut) beyond known activating variants remain unclear. We aimed to establish a translational research platform to characterize FGFR alterations (alt) and explore their potential as predictive biomarkers for FGFR-targeted agents. EXPERIMENTAL DESIGN: This ambispective study included a retrospective analysis of patients with FGFR-alt tumors treated with selective FGFR inhibitors (FGFRi) and a prospective collection of longitudinal tumor samples. Patient-derived xenografts (PDX) were generated to investigate FGFRi mechanisms of action and resistance. Molecular characterization included genomic, transcriptomic, proteomic, and functional analyses using the Functional Annotation for Cancer Treatment (FACT) assay. RESULTS: Among 36 retrospectively analyzed patients, clinical benefit from FGFRis was observed in cases with FGFR mRNA overexpression or FGFR2/11q co-amp, but no association was found with the amplification levels. In archival tumor samples, exploratory proteomic analysis showed FGFR1-4 protein expression in 78% of FGFR1/2-amp tumors detected by fluorescence in situ hybridization. RNA sequencing identified a higher prevalence of FGFR mRNA overexpression than proteomic analysis. Among patients harboring FGFR-mut, only one bladder cancer with an FGFR3-mut S249C derived benefit. FACT assay supported the functional activity of selected variants, including FGFR3 T689M, and suggested potential resistance mechanisms involving PI3K/PTEN and MAPK pathway co-alterations. A prospective FGFR-alt PDX biorepository enabled exploratory biomarker analyses, supporting the hypothesis that FGFR1-4 mRNA expression may better reflect FGFR dependency than genomic alterations alone. CONCLUSIONS: These findings highlight the complexity of FGFR-driven oncogenesis and support integrative molecular approaches to refine patient selection for FGFR-targeted therapies.

Humans↗
PubMed2026

Sequencing of Fibroblast Growth Factor Receptor Inhibitors in Cholangiocarcinoma: A Review of Published Cases.

Cholangiocarcinomas (CCAs) are aggressive biliary tumors that can develop within the intrahepatic (iCCA) or perihilar and distal bile ducts. The prognosis of patients with iCCA is poor due to its relative resistance to chemotherapy. Comprehensive genomic profiling of CCA biopsies by next-generation sequencing has revealed a rich landscape of genomic alterations, including fibroblast growth factor receptor (FGFR) gene fusions and rearrangements that are constitutively active and oncogenic. Several FGFR inhibitors (FGFRis) targeting these FGFR genomic alterations have been developed as potential treatments for iCCA, each of which are highly potent but differ in structure, mechanism of inhibition (ie, adenosine triphosphate-competitive reversible v covalent/irreversible v allosteric), pharmacologic/pharmacodynamic profiles, and selectivity for the four FGFR isoforms. Because of these differences, and due to resistance mutations acquired during FGFRi treatment, determining the optimal sequencing of FGFRis for the treatment of CCA remains contentious and is the subject of ongoing debate. To address this question, this review conducted an analysis of the literature on the FGFRi currently approved or in development, focusing on their distinct mechanisms of action and FGFR selectivity. Publicly available data from case reports on FGFRi sequencing in second and later lines of treatment were compiled from a PubMed search of published congress abstracts and articles. The results support a hypothesis that strategic sequencing of reversible followed by irreversible FGFRi may potentially prolong the duration of treatment benefit from FGFR inhibition compared with nonsequenced treatments. A hypothetical treatment-sequencing algorithm for reversible and irreversible FGFRi is discussed.

Humans↗