ArticleNeoplasia (New York, N.Y.)2012
Reduced efficacy of the Plk1 inhibitor BI 2536 on the progression of hepatocellular carcinoma due to low intratumoral drug levels.
Article in Neoplasia (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Preclinical Evaluation of Combined Polo-like Kinase 1 Inhibition and Navitoclax in Experimental Models of Lung Cancer.International journal of molecular sciences · 2026Article
- Druggable β-catenin palmitoyl-switch coordinates immune evasion via immunogenic ferroptosis resistance and PD-L1-mediated immunosuppression.Cell reports. Medicine · 2026Article
- Monoclonal Antibodies Accessing the Cytosol of Living Cells and Binding to Polo-Like Kinase 1 Interdomain Linker Affect Mitotic Behavior.Chembiochem : a European journal of chemical biology · 2026Article
- Co-administered internalizing RGD peptide boosts anti-PD-L1 therapy in hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2026Article
- Thymoquinone-conjugated liposomes improve cytotoxic and proapoptotic effects against hepatocellular cancer by altering the EGFR/ERK/MEK signaling axis.Discover oncology · 2025Article
- Tumour-specific activation of a tumour-blood transport improves the diagnostic accuracy of blood tumour markers in mice.EBioMedicine · 2024Article
- Leveraging the Fragment Molecular Orbital Method to Explore the PLK1 Kinase Binding Site and Polo-Box Domain for Potent Small-Molecule Drug Design.International journal of molecular sciences · 2023Article
- Assessment of the Pharmacokinetics, Disposition, and Duration of Action of the Tumour-Targeting Peptide CEND-1.International journal of molecular sciences · 2023Article
- Resistance to BRAF Inhibitors: EZH2 and Its Downstream Targets as Potential Therapeutic Options in Melanoma.International journal of molecular sciences · 2023Article
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- Hepatocellular Carcinoma Is a Natural Target for Adeno-Associated Virus (AAV) 2 Vectors.Cancers · 2022Article
- SETD3 Methyltransferase Regulates PLK1 Expression to PromoteFrontiers in oncology · 2022Article
- Exploration of Prognostic Biomarkers among Replication Factor C Family in the Hepatocellular Carcinoma.Evolutionary bioinformatics online · 2021Article
- Enhancing Gene-Knockdown Efficiency of Poly(ACS omega · 2018Article
- Combined effects of PLK1 and RAS in hepatocellular carcinoma reveal rigosertib as promising novel therapeutic "dual-hit" option.Oncotarget · 2018Article
- Article
- PLK1, A Potential Target for Cancer Therapy.Translational oncology · 2017Review
- TGF-β1 and TGF-β2 abundance in liver diseases of mice and men.Oncotarget · 2016Article
- Therapeutic targeting of polo-like kinase 1 using RNA-interfering nanoparticles (iNOPs) for the treatment of non-small cell lung cancer.Oncotarget · 2015Article
- Application of IL-36 receptor antagonist weakens CCL20 expression and impairs recovery in the late phase of murine acetaminophen-induced liver injury.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Highly promising preclinical data obtained in cultured cells and in nude mice bearing xenografts contrast with the rather modest clinical efficacy of Polo-like kinase 1 (Plk1) inhibitors. In the present study, we investigated if Plk1 might be a suitable target in hepatocellular carcinoma (HCC) and if a genetically engineered mouse tumor model that well reflects the tumor cell and micro-environmental features of naturally occurring cancers might be suitable to study anti-Plk1 therapy. Analysis of Plk1 expression in human HCC samples confirmed that HCC express much higher Plk1 levels than the adjacent normal liver tissue. Inhibition of Plk1 by an adenovirus encoding for a short hairpin RNA against Plk1 or by the small-molecule inhibitor BI 2536 reduced the viability of HCC cell lines and inhibited HCC xenograft progression in nude mice. Treatment of transforming growth factor (TGF) α/c-myc bitransgenic mice with BI 2536 during hepatocarcinogenesis reduced the number of dysplastic foci and of Ki-67-positive cells within the foci, indicating diminished tumorigenesis. In contrast, BI 2536 had no significant effect on HCC progression in the transgenic mouse HCC model as revealed by magnetic resonance imaging. Measurement of BI 2536 by mass spectrometry revealed considerably lower BI 2536 levels in HCC compared with the adjacent normal liver tissue. In conclusion, low intratumoral levels are a novel mechanism of resistance to the Plk1 inhibitor BI 2536. Plk1 inhibitors achieving sufficient intratumoral levels are highly promising in HCC treatment.
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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.