ArticleJCI insight2022
Targeting BCL-XL in fibrolamellar hepatocellular carcinoma.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- The Combination of a BCL-xL PROTAC and an mTOR Inhibitor Sensitizes Pancreatic Ductal Adenocarcinoma to KRASCancers · 2026Article
- PROTAC-mediated degradation of Bcl-xL potentiates target therapy in preclinical melanoma models.Journal of experimental & clinical cancer research : CR · 2026Article
- The combination of BCL-xL PROTAC and mTOR inhibitor sensitizes pancreatic ductal adenocarcinoma to KRASbioRxiv : the preprint server for biology · 2026Article
- AI-aided identification of dual-purpose therapeutic targets PRPF19 and MAPK9 in hepatocellular carcinoma and cellular senescence.npj aging · 2025Article
- First in human phase 1 study of DT2216, a selective BCL-xL degrader, in patients with relapsed/refractory solid malignancies.Journal of hematology & oncology · 2025Article
- The latest progress of personalized drug screening and therapy research for common clinical tumors through the PDX model platform.Journal of pharmaceutical analysis · 2025Review
- Article
- Chemical Evolution of Aplithianine Class of Serine/Threonine Kinase Inhibitors.Journal of medicinal chemistry · 2025Article
- DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming.Cancer discovery · 2025Article
- Protein isoform-centric therapeutics: expanding targets and increasing specificity.Nature reviews. Drug discovery · 2024Review
- 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
- Article
- Children's Oncology Group's 2023 blueprint for research: Liver tumors.Pediatric blood & cancer · 2023Article
- Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma.Science advances · 2023Article
- Fighting rare cancers: lessons from fibrolamellar hepatocellular carcinoma.Nature reviews. Cancer · 2023Review
- Current Advances in the Treatment of Fibrolamellar Carcinoma of Liver.Journal of hepatocellular carcinoma · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 1 country.
Funding
Abstract
Fibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal liver cancer with no proven effective systemic therapy. Inhibition of the antiapoptotic protein BCL-XL was found to synergize with a variety of systemic therapies in vitro using cells dissociated from patient-derived xenografts (PDX) of FLC or cells dissociated directly from surgical patient resections. As BCL-XL is physiologically expressed in platelets, prior efforts to leverage this vulnerability in other cancers have been hampered by severe thrombocytopenia. To overcome this toxicity, we treated FLC models with DT2216, a proteolysis targeting chimera (PROTAC) that directs BCL-XL for degradation via the von Hippel-Lindau (VHL) E3 ligase, which is minimally expressed in platelets. The combination of irinotecan and DT2216 in vitro on cells directly acquired from patients or in vivo using several xenografts derived from patients with FLC demonstrated remarkable synergy and at clinically achievable doses not associated with significant thrombocytopenia.
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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.