ArticleBiomolecules2019
The Lysosomal Sequestration of Tyrosine Kinase Inhibitors and Drug Resistance.
Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04394416 (Randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults With COVID-19), which is not on this map. Cited by 14 papers.
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.
Randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults With COVID-19
Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.Immunology · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Two decades of research on drug resistance in renal cell carcinoma.Discover oncology · 2026Article
- Quantitative Modeling of Lipid Droplet Contribution to Intracellular Drug Distribution and Efficacy of Tyrosine Kinase Inhibitors.ACS omega · 2026Article
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- Lysosomal Drug Sequestration Mediated by ABC Transporters and Drug Resistance.Pharmaceutics · 2025Article
- Lysosome targeted therapies in hematological malignancies.Frontiers in oncology · 2025Review
- Facilitated Transport of EGFR Inhibitors Plays an Important Role in Their Cellular Uptake.Analytical chemistry · 2024Article
- Measuring Tumour Imatinib Concentrations in Gastrointestinal Stromal Tumours: Relevant or Redundant?Cancers · 2023Article
- Review
- Small molecule photocatalysis enables drug target identification via energy transfer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Gefitinib induces EGFR and α5β1 integrin co-endocytosis in glioblastoma cells.Cellular and molecular life sciences : CMLS · 2021Article
- Lysosomal Biogenesis and Implications for Hydroxychloroquine Disposition.The Journal of pharmacology and experimental therapeutics · 2021Article
- Lysosomal Fusion: An Efficient Mechanism Increasing Their Sequestration Capacity for Weak Base Drugs without Apparent Lysosomal Biogenesis.Biomolecules · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Lysosomal sequestration of weak-base anticancer drugs is one putative mechanism for resistance to chemotherapy but it has never been directly proven. We addressed the question of whether the lysosomal sequestration of tyrosine kinase inhibitors (TKIs) itself contributes to the drug resistance in vitro. Our analysis indicates that lysosomal sequestration of an anticancer drug can significantly reduce the concentration at target sites, only when it simultaneously decreases its extracellular concentration due to equilibrium, since uncharged forms of weak-base drugs freely diffuse across cellular membranes. Even though the studied TKIs, including imatinib, nilotinib, and dasatinib, were extensively accumulated in the lysosomes of cancer cells, their sequestration was insufficient to substantially reduce the extracellular drug concentration. Lysosomal accumulation of TKIs also failed to affect the Bcr-Abl signaling. Cell pre-treatment with sunitinib significantly enhanced the lysosomal accumulation of the TKIs used; however, without apparent lysosomal biogenesis. Importantly, even increased lysosomal sequestration of TKIs neither decreased their extracellular concentrations nor affected the sensitivity of Bcr-Abl to TKIs. In conclusion, our results clearly show that the lysosomal sequestration of TKIs failed to change their concentrations at target sites, and thus, can hardly contribute to drug resistance in vitro.
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