Evidence map›Paper›PMID 39132655›Full record

ArticleGastro hep advances2023

Evaluation of Protein Kinase cAMP-Activated Catalytic Subunit Alpha as a Therapeutic Target for Fibrolamellar Carcinoma.

Stefanie S Schalm, Erin O'Hearn, Kevin Wilson, Timothy P LaBranche, Grace Silva, Zhuo Zhang, Lucian DiPietro, Neil Bifulco, Richard Woessner, Nicolas Stransky and 12 more

Abstract read
In one paragraph

Article in Gastro hep advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. A PKA-selective inhibitor captures an open but more ordered conformation of the PKA catalytic subunit.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. The COX2-PGEbioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Therapeutic, Clinicopathological, and Molecular Correlates ofPharmaceuticals (Basel, Switzerland) · 2024
    Article
  11. Article
  12. 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

22 authors.

Stefanie S SchalmBlueprint Medicines Corporation, Cambridge, Massachusetts.
Erin O'HearnBlueprint Medicines Corporation, Cambridge, Massachusetts.
Kevin WilsonBlueprint Medicines Corporation, Cambridge, Massachusetts.
Timothy P LaBrancheBlueprint Medicines Corporation, Cambridge, Massachusetts.
Grace SilvaBlueprint Medicines Corporation, Cambridge, Massachusetts.
Zhuo ZhangBlueprint Medicines Corporation, Cambridge, Massachusetts.
Lucian DiPietroBlueprint Medicines Corporation, Cambridge, Massachusetts.
Neil BifulcoBlueprint Medicines Corporation, Cambridge, Massachusetts.
Richard WoessnerBlueprint Medicines Corporation, Cambridge, Massachusetts.
Nicolas StranskyBlueprint Medicines Corporation, Cambridge, Massachusetts.
Darshan SappalBlueprint Medicines Corporation, Cambridge, Massachusetts.
Robert CampbellBlueprint Medicines Corporation, Cambridge, Massachusetts.
Riadh LobbardiBlueprint Medicines Corporation, Cambridge, Massachusetts.
Michael PalmerBlueprint Medicines Corporation, Cambridge, Massachusetts.
Joseph KimBlueprint Medicines Corporation, Cambridge, Massachusetts.
Chaoyang YeBlueprint Medicines Corporation, Cambridge, Massachusetts.
Marion DorschBlueprint Medicines Corporation, Cambridge, Massachusetts.
Christoph LengauerBlueprint Medicines Corporation, Cambridge, Massachusetts.
Timothy GuziBlueprint Medicines Corporation, Cambridge, Massachusetts.
Vivek KadambiBlueprint Medicines Corporation, Cambridge, Massachusetts.
Andrew GarnerBlueprint Medicines Corporation, Cambridge, Massachusetts.
Klaus P HoeflichBlueprint Medicines Corporation, Cambridge, Massachusetts.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 Methods: FLC patient-derived xenograft (PDX) shRNA cell lines were implanted subcutaneously into female NOD-SCID mice and tumors were allowed to develop prior to randomization to doxycycline (to induce knockdown) or control groups. Tumor development was assessed every 2 days. To assess the effect of treatment with novel selective PRKACA small molecule kinase inhibitors, BLU0588 and BLU2864, FLC PDX tumor cells were implanted subcutaneously into NOD-SCID mice and tumors allowed to develop. Mice were randomized to treatment (BLU0588 and BLU2864, orally, once daily) or control groups and tumor size determined as previously. Results: Knockdown of DNAJB1-PRKACA reversed a FLC-specific gene signature and reduced PDX tumor growth in mice compared to the control group. Furthermore, FLC PDX tumor growth was significantly reduced with BLU0588 and BLU2864 treatment vs control ( Conclusion: We demonstrated, using an inducible knockdown and small molecule approaches, that FLC PDX tumors were dependent upon DNAJB1-PRKACA fusion activity. In addition, this study serves as a proof-of-concept that PRKACA is a viable therapeutic target for FLC and warrants further investigation.

Indexed as

DNAJB1-PRKACAFibrolamellar carcinomaKinase inhibitorPRKACA

Identifiers

PMID39132655
PMCPMC11307690

What OpenQuestion holds

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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.