Evidence map›Paper›PMID 41205756›Full record

ArticleJournal of hepatology2026

DNAJ-PKAc induces metabolic rewiring and enhanced glutamine flux in fibrolamellar HCC.

Zeal Kamdar, Ethan Neumann, Kathryn Howe, Donald Long, Waqar Arif, Daniel H Shu, Aditya Mohan, Emma Kartalia, Jeric Hernandez, Solomon Levin and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Zeal KamdarDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ethan NeumannDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kathryn HoweDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Donald LongDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Waqar ArifDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daniel H ShuDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Aditya MohanDepartment of Neurosurgery, Duke University School of Medicine, Durham, NC, USA.
Emma KartaliaDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeric HernandezDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Solomon LevinDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kylie BelangerDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kayla BendinelliDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tamara Y Lopez-VidalDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
James M LeathermanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kabeer MunjalDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cissy ZhangGigantest, Baltimore, MD, USA.
Pratik KhareGigantest, Baltimore, MD, USA.
Paul G ThomasDepartments of Immunology and Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA.
Daniel J ZabranskyDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Won Jin HoDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Robert D LeoneDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Robert A AndersDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Anne LeGigantest, Baltimore, MD, USA.
Praveen SethupathyDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Chi V DangDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Elizabeth M JaffeeDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mark YarchoanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: mark.yarchoan@jhmi.edu.

Funding

Neoantigen-specific T cell responses for Fibrolamellar Hepatocellular CarcinomaR01CA265009 · NCI · JOHNS HOPKINS UNIVERSITY · PI Paul G. Thomas, Mark Yarchoan · 2022 to 2026
$3.6M
Neoadjuvant Immunotherapy Platform Study Reveals Mechanisms of Response in Hepatocellular Carcinoma (HCC)R01CA285544 · NCI · JOHNS HOPKINS UNIVERSITY · PI Won Jin Ho, Mark Yarchoan · 2024 to 2026
$2.0M
Exploiting A Critical Vulnerability To Glutamine Antimetabolite Therapy in Fibrolamellar Hepatocellular Carcinoma (FLC)R01CA289041 · NCI · JOHNS HOPKINS UNIVERSITY · PI Mark Yarchoan · 2024 to 2026
$1.9M
NCI NIH HHS R01 CA265009NCI NIH HHS R01 CA285544NCI NIH HHS R01 CA289041
6 · The paper itself

Abstract

BACKGROUND &

aimsFibrolamellar carcinoma (FLC) is a pediatric and adolescent liver cancer that is characterized by a recurrent fusion of DNAJB1 and PRKACA, yielding a chimeric translated protein, DNAJ-PKAc. PRKACA encodes the catalytic subunit of protein kinase A (PKA), a regulator of cellular metabolism.

methodsWe generated a syngeneic murine model of FLC, TIBx

resultsDNAJ-PKAc induced a high glycolytic and glutamine flux to support nucleotide metabolism. As compared to parental TIBx tumors, TIBx

conclusionThe presence of DNAJ-PKAc creates a vulnerability to the combination of glutamine antimetabolite and immune checkpoint inhibitor therapy in FLC. IMPACT AND IMPLICATIONS: The DNAJ-PKAc fusion in fibrolamellar carcinoma induces metabolic reprogramming, including enhanced glutamine metabolism, which promotes immune evasion. Targeting this metabolic vulnerability with a glutamine antagonist, in combination with immune checkpoint inhibitors, reverses the immunosuppressive tumor microenvironment, offering a promising therapeutic strategy for fibrolamellar carcinoma treatment.

Indexed as

Carcinoma, HepatocellularCyclic AMP-Dependent Protein Kinase Catalytic SubunitsGlutamineHSP40 Heat-Shock ProteinsLiver NeoplasmsAnimalsDisease Models, AnimalHumansImmune Checkpoint InhibitorsMiceCyclic AMP-Dependent Protein Kinase Catalytic SubunitsDNAJB1 protein, humanGlutamineHSP40 Heat-Shock ProteinsImmune Checkpoint InhibitorsPRKACA protein, humanFibrolamellarFLCglutaminehepatocellularimmunometabolismimmunotherapy

Identifiers

PMID41205756
PMCPMC13150750

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Registered trials

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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.