ArticleOncogene2019
Lysosomal trapping of palbociclib and its functional implications.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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
55 citing papers in PubMed, 90 citations in OpenAlex.
- Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline.Nature aging · 2026Article
- Divergent neuropsychiatric and systemic toxicity profiles of abemaciclib and palbociclib: a triangulation study integrating pharmacovigilance, genetic epidemiology, and multi-omics profiling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Multimodal imaging reveals a lysosomal drug reservoir that drives heterogeneous distribution of PARP inhibitors.Nature communications · 2026Article
- Mitochondrial bioenergetics-SASP crosstalk determines senolytic efficacy in therapy-induced senescence.Cell death discovery · 2026Article
- Senotoxins target senescence via lipid binding specificity, ion imbalance and lipidome remodeling.Nature aging · 2026Article
- Impact of Single Halogen Atom Substitutions on Antiviral Profile of Inhibitors Targeting SARS-CoV‑2 Main Protease.ACS omega · 2026Article
- Supramolecular Organogels Based on Cinnarizine as a Potential Gastroretentive System: In Vitro and In Silico Simulations.Gels (Basel, Switzerland) · 2026Article
- Metformin sensitizes non-small cell lung cancer to CDK4/6 inhibitor treatment by reducing lysosomal trapping.Science China. Life sciences · 2026Article
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- Investigating Metal and Fluorophore Controlled Intracellular Localization in Noble Metal Thiosemicarbazone Complexes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Targeting CyclinD1-CDK6 to Mitigate Senescence-Driven Inflammation and Age-Associated Functional Decline.bioRxiv : the preprint server for biology · 2025Article
- Advancements in antibody-drug conjugates as cancer therapeutics.Journal of the National Cancer Center · 2025Review
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Development of CDK4/6 Inhibitors in Gastrointestinal Cancers: Biomarkers to Move Forward.Current issues in molecular biology · 2025Review
- CDK4/6 inhibitor-associated vortex keratopathy: a case report.BMC ophthalmology · 2025Article
- Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies.Cell death discovery · 2025Article
- Oligoethylene Phosphoramidate-Based Kinase Inhibitor Prodrugs - Solubility, Enzyme Inhibition, and Hydrolysis.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Inducing Cellular Senescence in Mouse Embryonic Fibroblasts (MEFs).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Ocular toxicity events of cyclin-dependent kinase 4/6 inhibitors in breast cancer: a pharmacovigilance study based on the faers database.Frontiers in pharmacology · 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
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) approved for the treatment of some cancers. The main mechanism of action of palbociclib is to induce cell cycle arrest and senescence on responsive cells. Here, we report that palbociclib concentrates in intracellular acidic vesicles, where it can be readily observed due to its intrinsic fluorescence, and it is released from these vesicles upon dilution or washing out of the extracellular medium. This reversible storage of drugs into acidic vesicles is generally known as lysosomal trapping and, based on this, we uncover novel properties of palbociclib. In particular, a short exposure of cells to palbociclib is sufficient to produce a stable cell-cycle arrest and long-term senescence. Moreover, after washing out the drug, palbociclib-treated cells release the drug to the medium and this conditioned medium is active on susceptible cells. Interestingly, cancer cells resistant to palbociclib also accumulate and release the drug producing paracrine senescence on susceptible cells. Finally, other lysosomotropic drugs, such as chloroquine, interfere with the accumulation of palbociclib into lysosomes, thereby reducing the minimal dose of palbociclib required for cell-cycle arrest and senescence. In summary, lysosomal trapping explains the prolonged temporal activity of palbociclib, the paracrine activity of exposed cells, and the cooperation with lysosomotropic drugs. These are important features that may help to improve the therapeutic dosing and efficacy of palbociclib. Finally, two other clinically approved CDK4/6 inhibitors, ribociclib and abemaciclib, present a similar behavior as palbociclib, suggesting that lysosomal trapping is a property common to all three clinically-approved CDK4/6 inhibitors.
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.