ArticleBreast cancer research and treatment2017
New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth.
Article in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- An Acrolein-Based Drug Delivery System Enables Tumor-Specific Sphingosine-1-Phosphate Targeting in Breast Cancer without Lymphocytopenia.Cancer research communications · 2025Article
- Enhancing Lung Recovery: Inhaled Poly(lactic-ACS nano · 2025Article
- Article
- Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer.International journal of molecular sciences · 2024Review
- Emerging Roles of Ceramides in Breast Cancer Biology and Therapy.International journal of molecular sciences · 2022Review
- Low-Intensity Focused Ultrasound-Augmented Multifunctional Nanoparticles for Integrating Ultrasound Imaging and Synergistic Therapy of Metastatic Breast Cancer.Nanoscale research letters · 2021Article
- The Importance of Sphingosine Kinase in Breast Cancer: A Potential for Breast Cancer Management.Cureus · 2021Review
- Review
- Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate.Biomolecules · 2020Review
- Fingolimod inhibits proliferation and epithelial-mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling.Bioscience reports · 2020Article
- Sphingosine Kinase 1 in Breast Cancer-A New Molecular Marker and a Therapy Target.Frontiers in oncology · 2020Review
- Chrysin and Docetaxel Loaded Biodegradable Micelle for Combination Chemotherapy of Cancer Stem Cell.Pharmaceutical research · 2019Article
- S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy.Molecular diagnosis & therapy · 2019Review
- Transcriptome-Wide Effects of Sphingosine Kinases Knockdown in Metastatic Prostate and Breast Cancer Cells: Implications for Therapeutic Targeting.Frontiers in pharmacology · 2019Article
- Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors.Breast cancer research and treatment · 2018Article
- Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq.Nature communications · 2018Article
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCombining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity.
methodsDocetaxel, FTY and glucosamine were covalently conjugated to poly(lactic-co-glycolic acid) (PLGA). NPs were characterised by dynamic light scattering and electron microscopy. The cellular uptake, cytotoxicity and in vivo antitumor efficacy of CNPs were evaluated.
resultsWe show for the first time that in triple negative breast cancer cells FTY provides chemosensitisation to DTX, allowing a four-fold reduction in the effective dose. We have encapsulated both drugs in PLGA complex NPs (CNPs), with narrow size distribution of ~ 100 nm and excellent cancer cell uptake providing sequential, sustained release of FTY and DTX. In triple negative breast cancer cells and mouse breast cancer models, CNPs had similar efficacy to systemic free therapies, but allowed an effective drug dose reduction. Application of CNPs has significantly reversed chemotherapy side effects such as weight loss, liver toxicity and, most notably, lymphopenia.
conclusionsWe show for the first time the DTX chemosensitising effects of FTY in triple negative breast cancer. We further demonstrate that encapsulation of free drugs in CNPs can improve targeting, provide low off-target toxicity and most importantly reduce FTY-induced lymphopenia, offering potential therapeutic use of FTY in clinical cancer 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.