ArticleInvestigational new drugs2012
The cytotoxic activity of Aplidin in chronic lymphocytic leukemia (CLL) is mediated by a direct effect on leukemic cells and an indirect effect on monocyte-derived cells.
Article in Investigational new drugs, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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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.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.Life science alliance · 2022Trial
- Role of histone deacetylases in blood cancer: Exploring peptide‑based inhibitors as therapeutic strategies for leukemia treatment (Review).Oncology reports · 2026Review
- Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.International journal of molecular sciences · 2025Review
- Unveiling the potential of marine peptides in leukemia: mechanistic insights and future horizon in peptide research.Turkish journal of medical sciences · 2025Review
- Modulation of the tumor microenvironment by natural agents: implications for cancer prevention and therapy.Seminars in cancer biology · 2022Review
- Novel molecules as the emerging trends in cancer treatment: an update.Medical oncology (Northwood, London, England) · 2022Review
- Marine Power on Cancer: Drugs, Lead Compounds, and Mechanisms.Marine drugs · 2021Review
- Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A.Science (New York, N.Y.) · 2021Article
- Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers.Cancer medicine · 2018Review
- Pharmacokinetics and excretion ofInvestigational new drugs · 2017Article
- An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs.Molecules (Basel, Switzerland) · 2017Review
- Plitidepsin: design, development, and potential place in therapy.Drug design, development and therapy · 2017Review
- Reprogramming Nurse-like Cells with Interferon γ to Interrupt Chronic Lymphocytic Leukemia Cell Survival.The Journal of biological chemistry · 2016Article
- Trabectedin and plitidepsin: drugs from the sea that strike the tumor microenvironment.Marine drugs · 2014Review
- Nurse-like cells control the activity of chronic lymphocytic leukemia B cells via galectin-1.Leukemia · 2013Article
- Article
- Marine invertebrate natural products for anti-inflammatory and chronic diseases.Evidence-based complementary and alternative medicine : eCAM · 2013Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aplidin is a novel cyclic depsipeptide, currently in Phase II/III clinical trials for solid and hematologic malignancies. The aim of this study was to evaluate the effect of Aplidin in chronic lymphocytic leukemia (CLL), the most common leukemia in the adult. Although there have been considerable advances in the treatment of CLL over the last decade, drug resistance and immunosuppression limit the use of current therapy and warrant the development of novel agents. Here we report that Aplidin induced a dose- and time-dependent cytotoxicity on peripheral blood mononuclear cells (PBMC) from CLL patients. Interestingly, Aplidin effect was markedly higher on monocytes compared to T lymphocytes, NK cells or the malignant B-cell clone. Hence, we next evaluated Aplidin activity on nurse-like cells (NLC) which represent a cell subset differentiated from monocytes that favors leukemic cell progression through pro-survival signals. NLC were highly sensitive to Aplidin and, more importantly, their death indirectly decreased neoplasic clone viability. The mechanisms of Aplidin-induced cell death in monocytic cells involved activation of caspase-3 and subsequent PARP fragmentation, indicative of death via apoptosis. Aplidin also showed synergistic activity when combined with fludarabine or cyclophosphamide. Taken together, our results show that Aplidin affects the viability of leukemic cells in two different ways: inducing a direct effect on the malignant B-CLL clone; and indirectly, by modifying the microenvironment that allows tumor growth.
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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.