ArticleNature communications2023
Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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.
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.
Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Molecular biomarkers for diagnosis, prognosis, precision therapy, and immunotherapy in cholangiocarcinoma, cHCC-CCA, and HCC.Hepatology communications · 2026Review
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- NEK7-induced phosphorylation of EGFR on serine 1070 drives the acquired lenvatinib resistance in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.Carcinogenesis · 2026Review
- Clinical Effectiveness of miR-760 to Distinguish Benign and Malignant Pulmonary Nodules on the Basis of Low-Dose Spiral CT Imaging.Molecular imaging and biology · 2026Article
- RPRD1A drives lenvatinib resistance in hepatocellular carcinoma via the ITGA5-FAK signaling axis.Molecular biomedicine · 2026Article
- Protein expression profiling of lenvatinib-resistant liver cancer cells and identify B4GALT4 as a critical drug resistance molecule.Discover oncology · 2026Article
- CDK4 inhibition by luteolin enhances lenvatinib sensitivity in HCC via Wnt/β-catenin modulation.Cancer cell international · 2026Article
- A bibliometric study on microenvironment-mediated drug resistance in interventional liver cancer treatment.Discover oncology · 2025Article
- Wild-type KRAS activation drives evasion of interferon-mediated immunity and resistance to immunotherapy in hepatocellular carcinoma.Nature communications · 2025Article
- Targeting immunosuppressive macrophages by CSRP2-regulated CCL28 signaling sensitizes hepatocellular carcinoma to lenvatinib.Journal for immunotherapy of cancer · 2025Article
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- Hyaluronic acid-tailored prodrug nanoplatforms for efficiently overcoming colorectal cancer chemoresistance and recurrence by synergistic inhibition of cancer cell stemness.Journal of nanobiotechnology · 2025Article
- Applications and techniques of single-cell RNA sequencing across diverse species.Briefings in bioinformatics · 2025Review
- Neoadjuvant treatment patterns and biomarker selection in muscle-invasive bladder cancer.Discover oncology · 2025Review
- Advances in sulfonyl exchange chemical biology: expanding druggable target space.Chemical science · 2025Review
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- Co-inhibition of RAGE and TLR4 sensitizes pancreatic cancer to irreversible electroporation in mice by disrupting autophagy.Acta pharmacologica Sinica · 2025Article
- Copper-mediated SEC14L3 promotes cuproptosis to inhibit hepatocellular carcinoma growth via ERK/YY1/FDX1 axis.Communications biology · 2025Article
- Lenvatinib-activated NDUFA4L2/IL33/PADI4 pathway induces neutrophil extracellular traps that inhibit cuproptosis in hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence has demonstrated that drug resistance can be acquired in cancer cells by kinase rewiring, which is an obstacle for efficient cancer therapy. However, it is technically challenging to measure the expression of protein kinases on large scale due to their dynamic range in human proteome. We employ a lysine-targeted sulfonyl fluoride probe, named XO44, which binds to 133 endogenous kinases in intact lenvatinib-resistant hepatocellular carcinoma (HCC) cells. This analysis reveals cyclin-dependent kinase 6 (CDK6) upregulation, which is mediated by ERK/YAP1 signaling cascade. Functional analyses show that CDK6 is crucial in regulation of acquired lenvatinib resistance in HCC via augmentation of liver cancer stem cells with clinical significance. We identify a noncanonical pathway of CDK6 in which it binds and regulates the activity of GSK3β, leading to activation of Wnt/β-catenin signaling. Consistently, CDK6 inhibition by palbociclib or degradation by proteolysis targeting chimeras (PROTACs) is highly synergistic with lenvatinib in vitro. Interestingly, palbociclib not only exerts maximal growth suppressive effect with lenvatinib in lenvatinib-resistant HCC models but also reshapes the tumor immune microenvironment. Together, we unveil CDK6 as a druggable target in lenvatinib-resistant HCC and highlight the use of a chemical biology approach to understand nongenetic resistance mechanisms in cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.