ArticleCancer discovery2021
Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening.
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 45 citations in OpenAlex.
- Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- A Pan-Cancer Ex Vivo Drug Screen Atlas for Functional Precision Oncology.bioRxiv : the preprint server for biology · 2026Article
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
- Metastatic Fibrolamellar Hepatocellular Carcinoma in a Young Adult: A Case Report and Narrative Review.Journal of hepatocellular carcinoma · 2026Article
- Advancing liver cancer diagnosis and treatment with multi-omics approaches: a systematic review.Discover oncology · 2025Review
- Article
- Chemical Evolution of Aplithianine Class of Serine/Threonine Kinase Inhibitors.Journal of medicinal chemistry · 2025Article
- Patient-derived xenograft model: Applications and challenges in liver cancer.Chinese medical journal · 2025Review
- PDX models for functional precision oncology and discovery science.Nature reviews. Cancer · 2025Review
- DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming.Cancer discovery · 2025Article
- Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma.Nature communications · 2024Article
- DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.Cancers · 2024Article
- Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1.Cancer research · 2024Article
- A preclinical "magic bullet" against fibrolamellar hepatocellular carcinoma?Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- GalNAc-conjugated siRNA targeting the DNAJB1-PRKACA fusion junction in fibrolamellar hepatocellular carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Models of fibrolamellar carcinomas, tools for evaluation of a new era of treatments.Frontiers in immunology · 2024Review
- Enzymatic Redox Properties and Cytotoxicity of Irreversible Nitroaromatic Thioredoxin Reductase Inhibitors in Mammalian Cells.International journal of molecular sciences · 2023Article
- Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma.Science advances · 2023Article
- Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss.Nature communications · 2023Article
Corrections and comments
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Authors and funding
36 authors at 13 institutions in 2 countries.
Funding
Abstract
To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the antiapoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable. SIGNIFICANCE: Therapeutics informed by genomics have not yielded effective therapies for FLC. A functional screen identified TOPO1, HDAC inhibitors, and napabucasin as efficacious and synergistic with inhibition of Bcl-xL. Validation on cells dissociated directly from patient tumors demonstrates the ability for functional precision medicine in a solid tumor.
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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.