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DOI: 10.1101/2023.03.12.23287041

Synergic activity of FGFR2 and MEK inhibitors in the treatment of FGFR2-amplified cancers of unknown primary

A.Cavazzoni I. Salamon C. Fumarola ...+23 M. Ferracin
摘要
Patients with cancer of unknown primary (CUP) carry the double burden of an aggressive disease and reduced access to therapies. Experimental models summing up CUP features are pivotal for CUP biology investigation and drug testing. We derived two CUP cell lines (CUP#55 and #96), and corresponding patient-derived xenografts (PDXs), from ascites tumor cells. CUP cell lines and PDXs underwent histological, immune-phenotypical, molecular, and genomic characterization confirming the features of the original tumor. Genetic testing and FISH analysis identified FGFR2 amplification as therapeutic target in tumor tissues and patient-derived models. Drug-screening assays were performed to test the activity of FGFR2 targeting drug BGJ-398 (infigratinib) and the combination treatment with the MEK inhibitor trametinib, which proved to be synergic and exceptionally active, both in vitro and in vivo. This study brings personalized therapy closer to CUP patients and paves the way to future applications of personalized medicine for metastatic patients with adverse prognosis.
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