ArticleGut2017
Palbociclib (PD-0332991), a selective CDK4/6 inhibitor, restricts tumour growth in preclinical models of hepatocellular carcinoma.
Article in Gut, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
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Who cites it
165 citing papers in PubMed, 291 citations in OpenAlex.
- Molecular Signaling Pathways, Regulatory and Coactivator Networks, and Emerging Mechanisms in Hepatocellular Carcinoma.Biomedicines · 2026Review
- Biallelic loss of RB1 in hepatocellular carcinoma as synthetic lethal target for artificial intelligence-guided therapy.Signal transduction and targeted therapy · 2026Article
- Novel nuclear RNA export factor 1 adaptor drives tumor growth by increasing proliferation-stimulatory mRNA export.Signal transduction and targeted therapy · 2026Article
- Chaperone-mediated autophagy is a tumor-suppressive mechanism in hepatocellular carcinoma.Cell reports · 2026Article
- Novel driver gene FIRRM regulates the cell cycle for promoting tumor growth in hepatocellular carcinoma.Journal of gastroenterology · 2026Article
- Review
- Pyrimidine-based compounds as promising anticancer agents targeting tumor cell senescence.Molecular therapy. Oncology · 2026Article
- Genome-wide screenings identify BAP1 as a synthetic-lethality target with CDK4/6 inhibitors.Science advances · 2026Article
- Drug-tolerant persister cells: the deadly survivors in hematological malignancies.Frontiers in pharmacology · 2026Review
- Glucose starvation mimetic aldometanib removes immune barriers permitting mice with hepatocellular carcinoma to live to normal ages.Cell research · 2025Article
- MicroRNA‑885‑5p regulates cell cycle progression in liver cancer cells.International journal of molecular medicine · 2025Article
- Cancer Cell Dormancy in the Bone Microenvironment.Current osteoporosis reports · 2025Review
- Efficacy of CDK4/6 Inhibition in colorectal cancer and the role of p16 expression in predicting drug resistance.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Article
- TOPK promotes immune suppression in kidney renal clear cell carcinoma and emerges as a prognostic and therapeutic target.BMC cancer · 2025Article
- The Non-Canonical ChREBPα Activity Suppresses the Activation of Hepatic Stellate Cells and Liver Fibrosis by Antagonizing TGF-β-E2F1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Safety and pharmacokinetics of FCN-437c, a novel cyclin-dependent kinase 4/6 inhibitor, in Chinese patients with hepatic impairment.Investigational new drugs · 2025Article
- CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.Journal of advanced research · 2025Article
- Review
- Development of CDK4/6 Inhibitors in Gastrointestinal Cancers: Biomarkers to Move Forward.Current issues in molecular biology · 2025Review
105 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveAdvanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Palbociclib, a well-tolerated and selective CDK4/6 inhibitor, has shown promising results in the treatment of retinoblastoma (RB1)-positive breast cancer. RB1 is rarely mutated in HCC, suggesting that palbociclib could potentially be used for HCC therapy. Here, we provide a comprehensive characterisation of the efficacy of palbociclib in multiple preclinical models of HCC.
designThe effects of palbociclib on cell proliferation, cellular senescence and cell death were investigated in a panel of human liver cancer cell lines, in ex vivo human HCC samples, in a genetically engineered mouse model of liver cancer, and in human HCC xenografts in vivo. The mechanisms of intrinsic and acquired resistance to palbociclib were assessed in human liver cancer cell lines and human HCC samples by protein and gene expression analyses.
resultsPalbociclib suppressed cell proliferation in human liver cancer cell lines by promoting a reversible cell cycle arrest. Intrinsic and acquired resistance to palbociclib was determined by loss of RB1. A signature of 'RB1 loss of function' was found in <30% of HCC samples. Palbociclib, alone or combined with sorafenib, the standard of care for HCC, impaired tumour growth in vivo and significantly increased survival.
conclusionsPalbociclib shows encouraging results in preclinical models of HCC and represents a novel therapeutic strategy for HCC treatment, alone or particularly in combination with sorafenib. Palbociclib could potentially benefit patients with RB1-proficient tumours, which account for 70% of all patients with HCC.
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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.