ArticleCancers2020
Extracellular Vesicle Delivery of TRAIL Eradicates Resistant Tumor Growth in Combination with CDK Inhibition by Dinaciclib.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.Journal of Cancer · 2024Review
- Intensity Interrogation-Based High-Sensitivity Surface Plasmon Resonance Imaging Biosensor for Apoptosis Detection in Cancer.Biosensors · 2023Article
- Cytochalasin B-Induced Membrane Vesicles from TRAIL-Overexpressing Mesenchymal Stem Cells Induce Extrinsic Pathway of Apoptosis in Breast Cancer Mouse Model.Current issues in molecular biology · 2023Article
- Exosomal delivery of TRAIL and miR‑335 for the treatment of hepatocellular carcinoma (Review).International journal of molecular medicine · 2023Review
- Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Immune Modulatory Effects of Molecularly Targeted Therapy and Its Repurposed Usage in Cancer Immunotherapy.Pharmaceutics · 2022Review
- Tumour Derived Extracellular Vesicles: Challenging Target to Blunt Tumour Immune Evasion.Cancers · 2022Review
- Pulmonary Delivery of Extracellular Vesicle-Encapsulated Dinaciclib as an Effective Lung Cancer Therapy.Cancers · 2022Article
- EV-T synergizes with AZD5582 to overcome TRAIL resistance through concomitant suppression of cFLIP, MCL-1, and IAPs in hepatocarcinoma.Journal of molecular medicine (Berlin, Germany) · 2022Article
- MSC-Derived Extracellular Vesicle-Delivered L-PGDS Inhibit Gastric Cancer Progression by Suppressing Cancer Cell Stemness and STAT3 Phosphorylation.Stem cells international · 2022Article
- Article
- Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma-backbone or add-on in immune-oncology?Cancer metastasis reviews · 2021Review
- Suppression of Ovarian Cancer Cell Growth by AT-MSC Microvesicles.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) is a promising anti-cancer agent that rapidly induces apoptosis in cancer cells. Unfortunately, the clinical application of recombinant TRAIL (rTRAIL) has been hampered by its common cancer resistance. Naturally TRAIL is delivered as a membrane-bound form by extracellular vesicles (EV-T) and is highly efficient for apoptosis induction. SCH727965 (dinaciclib), a potent cyclin-dependent kinase (CDK) inhibitor, was shown to synergize with other drugs to get better efficacy. However, it has never been investigated if dinaciclib coordinates with EV-T to enhance therapeutic results. This study explores the potential of combination therapy with EV-T and dinaciclib for cancer treatment. EV-T was successfully derived from human TRAIL transduced cells and shown to partially overcome resistance of A549 cells. Dinaciclib was shown to drastically enhance EV-T killing effects on cancer lines that express good levels of death receptor (DR) 5, which are associated with suppression of CDK1, CDK9 and anti-apoptotic proteins. Combination therapy with low doses of EV-T and dinaciclib induced strikingly enhanced apoptosis and led to complete regression in A549 tumors without any adverse side effects observed in a subcutaneous xenograft model. Tumor infiltration of mass NK cells and macrophages was also observed. These observations thus indicate that the combination of EV-T with dinaciclib is a potential novel therapy for highly effective and safe cancer treatment.
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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.