Publications by authors named "N Bifulco"

Background And Aims: Fibrolamellar carcinoma (FLC) is a rare, difficult-to-treat liver cancer primarily affecting pediatric and adolescent patients, and for which precision medicine approaches have historically not been possible. The gene fusion was identified as a driver of FLC pathogenesis. We aimed to assess whether FLC tumors maintain dependency on this gene fusion and determine if PRKACA is a viable therapeutic target.

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Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide with no clinically confirmed oncogenic driver. Although preclinical studies implicate the FGF19 receptor FGFR4 in hepatocarcinogenesis, the dependence of human cancer on FGFR4 has not been demonstrated. Fisogatinib (BLU-554) is a potent and selective inhibitor of FGFR4 and demonstrates clinical benefit and tumor regression in patients with HCC with aberrant FGF19 expression.

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Multidrug-resistant (MDR) bacterial infections are a serious threat to public health. Among the most alarming resistance trends is the rapid rise in the number and diversity of β-lactamases, enzymes that inactivate β-lactams, a class of antibiotics that has been a therapeutic mainstay for decades. Although several new β-lactamase inhibitors have been approved or are in clinical trials, their spectra of activity do not address MDR pathogens such as Acinetobacter baumannii.

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Article Synopsis
  • Aberrant signaling of the FGF19/FGFR4 complex is linked to hepatocellular carcinoma (HCC) in both mice and potentially humans, prompting the development of a targeted therapy.
  • BLU9931 is a selective and irreversible small-molecule inhibitor specifically targeting FGFR4, showing strong anti-tumor effects in HCC models with overexpressed FGF19.
  • About one-third of HCC patients with FGF19, FGFR4, and its coreceptor KLB may benefit from BLU9931 treatment, marking a significant advancement in targeted therapy for this cancer type.
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A series of oxazole-substituted indanylacetic acids were prepared which show a spectrum of activity as ligands for PPAR nuclear receptor subtypes.

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