ArticleInternational journal of cancer2020
Lipid droplet-mediated scavenging as novel intrinsic and adaptive resistance factor against the multikinase inhibitor ponatinib.
Article in International journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Genes and Pathways Involved in the Progression of Malignant Pleural Mesothelioma: A Meta-analysis of Genome-Wide Expression Studies.Biochemical genetics · 2024Pooled it
- Lipid droplets as stress-buffering organelles in cancer cell homeostasis.Communications biology · 2026Review
- Quantitative Modeling of Lipid Droplet Contribution to Intracellular Drug Distribution and Efficacy of Tyrosine Kinase Inhibitors.ACS omega · 2026Article
- Liquid-liquid phase separation in cancer therapy resistance.iScience · 2026Review
- Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy.Pharmaceutics · 2024Review
- Fibroblast growth receptor 1 is regulated by G-quadruplex in metastatic breast cancer.Communications biology · 2024Article
- Phospholipid Acyltransferases: Characterization and Involvement of the Enzymes in Metabolic and Cancer Diseases.Cancers · 2024Review
- Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Review
- The Lipid Metabolism as Target and Modulator of BOLD-100 Anticancer Activity: Crosstalk with Histone Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways.International journal of molecular sciences · 2023Article
- Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors.Cell death & disease · 2022Article
- The BASHY Platform Enables the Assembly of a Fluorescent Bortezomib-GV1001 Conjugate.ACS medicinal chemistry letters · 2022Article
- Novel Insights on Lipid Metabolism Alterations in Drug Resistance in Cancer.Frontiers in cell and developmental biology · 2022Review
- Microtubule motor driven interactions of lipid droplets: Specificities and opportunities.Frontiers in cell and developmental biology · 2022Review
- Lipid droplet evolution gives insight into polyaneuploid cancer cell lipid droplet functions.Medical oncology (Northwood, London, England) · 2021Review
- Development of a cobalt(iii)-based ponatinib prodrug system.Inorganic chemistry frontiers · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Ponatinib is a small molecule multi-tyrosine kinase inhibitor clinically approved for anticancer therapy. Molecular mechanisms by which cancer cells develop resistance against ponatinib are currently poorly understood. Likewise, intracellular drug dynamics, as well as potential microenvironmental factors affecting the activity of this compound are unknown. Cell/molecular biological and analytical chemistry methods were applied to investigate uptake kinetics/subcellular distribution, the role of lipid droplets (LDs) and lipoid microenvironment compartments in responsiveness of FGFR1-driven lung cancer cells toward ponatinib. Selection of lung cancer cells for acquired ponatinib resistance resulted in elevated intracellular lipid levels. Uncovering intrinsic ponatinib fluorescence enabled dissection of drug uptake/retention kinetics in vitro as well as in mouse tissue cryosections, and revealed selective drug accumulation in LDs of cancer cells. Pharmacological LD upmodulation or downmodulation indicated that the extent of LD formation and consequent ponatinib incorporation negatively correlated with anticancer drug efficacy. Co-culturing with adipocytes decreased ponatinib levels and fostered survival of cancer cells. Ponatinib-selected cancer cells exhibited increased LD levels and enhanced ponatinib deposition into this organelle. Our findings demonstrate intracellular deposition of the clinically approved anticancer compound ponatinib into LDs. Furthermore, increased LD biogenesis was identified as adaptive cancer cell-defense mechanism via direct drug scavenging. Together, this suggests that LDs represent an underestimated organelle influencing intracellular pharmacokinetics and activity of anticancer tyrosine kinase inhibitors. Targeting LD integrity might constitute a strategy to enhance the activity not only of ponatinib, but also other clinically approved, lipophilic anticancer therapeutics.
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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.