ArticleGut2025
DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma.
Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Neuroepithelial reprogramming and ERBB vulnerability in canine acanthomatous ameloblastoma.Molecular therapy. Oncology · 2026Article
- Transcriptional states define dependencies and therapeutic vulnerabilities in head and neck cancer.NPJ precision oncology · 2026Article
- Machine learning-based early survival prediction in early-onset hepatocellular carcinoma: a SEER-based multi-model comparative study.Translational cancer research · 2026Article
- Subtype-Specific Dependencies and Drug Vulnerabilities Enable Precision Therapeutics in Head and Neck Cancer.bioRxiv : the preprint server for biology · 2025Article
- Drug screening in 3D microtumors reveals DDR1/2-MAPK12-GLI1 as a vulnerability in cancer-associated fibroblasts.Cell reports. Medicine · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundFibrolamellar carcinoma (FLC), a rare and fatal liver cancer lacking effective drug therapy, is driven by the DNAJ-PKAc fusion oncoprotein. However, the underlying mechanism of DNAJ-PKAc's role in FLC tumour growth remains enigmatic.
objectiveWe sought to determine the protein kinase-mediated signalling networks that drive growth and proliferation in FLC.
designWe integrated a combination of newly established preclinical models of FLC and an unbiased polypharmacology-based approach to identify downstream kinases involved in DNAJ-PKAc-mediated FLC cell growth. We validated our findings in multiple patient-derived mouse models and patient tumours.
resultsFunctional screening, coupled with computational analysis, highlighted Polo-like kinase 1 (PLK1) as vital for FLC cell viability. Genetic and pharmacological PLK1 inhibition significantly reduced FLC cell growth, inducing apoptosis. Further studies showed DNAJ-PKAc's centrosomal presence and direct interaction with PLK1, revealing a novel mechanism that promotes PLK1 activation and mitotic progression. Clinical-grade PLK1 inhibitors effectively suppressed FLC tumour growth across multiple preclinical models, including patient-derived xenograft and an orthotopic model of FLC, suggesting promising therapeutic avenues.
conclusionOur findings underscore the role of DNAJ-PKAc in rewiring signalling networks and highlight valuable clinical implications for PLK1-targeted therapies for FLC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.