ArticleOncotarget2016
Reversal of the glycolytic phenotype of primary effusion lymphoma cells by combined targeting of cellular metabolism and PI3K/Akt/ mTOR signaling.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Metabolic Interactions in the Tumor Microenvironment of Classical Hodgkin Lymphoma: Implications for Targeted Therapy.International journal of molecular sciences · 2025Review
- Metabolic deficiencies underlie reduced plasmacytoid dendritic cell IFN-I production following viral infection.Nature communications · 2025Article
- Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.International journal of molecular sciences · 2023Review
- Mechanisms Involved in the Promoting Activity of Fibroblasts in HTLV-1-Mediated Lymphomagenesis: Insights into the Plasticity of Lymphomatous Cells.International journal of molecular sciences · 2021Article
- Cancer cell metabolic plasticity in migration and metastasis.Clinical & experimental metastasis · 2021Review
- Molecular profiling reveals a hypoxia signature in breast implant-associated anaplastic large cell lymphoma.Haematologica · 2021Article
- Metabolic heterogeneity and immunocompetence of infiltrating immune cells in the breast cancer microenvironment (Review).Oncology reports · 2021Review
- Non-Hodgkin Lymphoma Metabolism.Advances in experimental medicine and biology · 2021Article
- Review
- Kinome profiling of non-Hodgkin lymphoma identifies Tyro3 as a therapeutic target in primary effusion lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review).Molecular medicine reports · 2019Review
- Epstein-Barr Virus-Induced Metabolic Rearrangements in Human B-Cell Lymphomas.Frontiers in microbiology · 2018Review
- Propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR/p70S6K signaling pathway in melanoma cells.Oncology letters · 2018Article
- Regulation of glucose uptake in lymphoma cell lines by c-MYC- and PI3K-dependent signaling pathways and impact of glycolytic pathways on cell viability.Journal of translational medicine · 2017Article
- Ataxia-Telangiectasia Mutated Modulation of Carbon Metabolism in Cancer.Frontiers in oncology · 2017Review
- Anticancer strategies based on the metabolic profile of tumor cells: therapeutic targeting of the Warburg effect.Acta pharmacologica Sinica · 2016Review
- Non-Hodgkin Lymphoma Metabolism.Advances in experimental medicine and biologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PEL is a B-cell non-Hodgkin lymphoma, occurring predominantly as a lymphomatous effusion in body cavities, characterized by aggressive clinical course, with no standard therapy. Based on previous reports that PEL cells display a Warburg phenotype, we hypothesized that the highly hypoxic environment in which they grow in vivo makes them more reliant on glycolysis, and more vulnerable to drugs targeting this pathway. We established here that indeed PEL cells in hypoxia are more sensitive to glycolysis inhibition. Furthermore, since PI3K/Akt/mTOR has been proposed as a drug target in PEL, we ascertained that pathway-specific inhibitors, namely the dual PI3K and mTOR inhibitor, PF-04691502, and the Akt inhibitor, Akti 1/2, display improved cytotoxicity to PEL cells in hypoxic conditions. Unexpectedly, we found that these drugs reduce lactate production/extracellular acidification rate, and, in combination with the glycolysis inhibitor 2-deoxyglucose (2-DG), they shift PEL cells metabolism from aerobic glycolysis towards oxidative respiration. Moreover, the associations possess strong synergistic cytotoxicity towards PEL cells, and thus may reduce adverse reaction in vivo, while displaying very low toxicity to normal lymphocytes. Finally, we showed that the association of 2-DG and PF-04691502 maintains its cytotoxic and proapoptotic effect also in PEL cells co-cultured with human primary mesothelial cells, a condition known to mimic the in vivo environment and to exert a protective and pro-survival action. All together, these results provide a compelling rationale for the clinical development of new therapies for the treatment of PEL, based on combined targeting of glycolytic metabolism and constitutively activated signaling pathways.
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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.