ArticleOncotarget2015
Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Role of indoleamine 2, 3-dioxygenase 1 in immunosuppression of breast cancer.Cancer pathogenesis and therapy · 2024Review
- Review
- The MEK/ERK Network as a Therapeutic Target in Human Cancer.Molecular cancer research : MCR · 2021Review
- Control of adipogenic commitment by a STAT3-VSTM2A axis.American journal of physiology. Endocrinology and metabolism · 2021Article
- Hypoxia, endoplasmic reticulum stress and chemoresistance: dangerous liaisons.Journal of experimental & clinical cancer research : CR · 2021Review
- Overcoming drug resistance in glioblastoma: new options in sight?Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Review
- Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review.BMC cancer · 2020Review
- Article
- New horizons from novel therapies in malignant pleural mesothelioma.Advances in respiratory medicine · 2020Review
- ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer.International journal of molecular sciences · 2019Review
- Zoledronic acid blocks the interaction between breast cancer cells and regulatory T-cells.BMC cancer · 2019Article
- The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy.Frontiers in oncology · 2019Review
- Pyruvate Treatment Restores the Effectiveness of Chemotherapeutic Agents in Human Colon Adenocarcinoma and Pleural Mesothelioma Cells.International journal of molecular sciences · 2018Article
- Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?European respiratory review : an official journal of the European Respiratory Society · 2018Review
- Immune modulation of CD4BMC immunology · 2016Article
- Cancer-associated fibroblast suppresses killing activity of natural killer cells through downregulation of poliovirus receptor (PVR/CD155), a ligand of activating NK receptor.International journal of oncology · 2016Article
- Icmt inhibition exerts anti-angiogenic and anti-hyperpermeability activities impeding malignant pleural effusion.Oncotarget · 2016Article
- Article
- Understanding the role of the kynurenine pathway in human breast cancer immunobiology.Oncotarget · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells.
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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.