ArticleOncotarget2017
Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Pooled it
- Review
- New power in cancer immunotherapy: the rise of chimeric antigen receptor macrophage (CAR-M).Journal of translational medicine · 2025Review
- Setup of an In Vitro Three-Dimensional Stromalized Prostate Cancer Model Using Gelatin Microparticles.ACS omega · 2025Article
- Targeting the tumor microenvironment, a new therapeutic approach for prostate cancer.Prostate cancer and prostatic diseases · 2025Review
- Review
- Chlorogenic Acid as a Potential Therapeutic Agent for Cholangiocarcinoma.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Mechanism exploration of Zoledronic acid combined with PD-1 in the treatment of hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2024Article
- Reprogramming the tumor microenvironment to improve the efficacy of cancer immunotherapies.Medical oncology (Northwood, London, England) · 2022Review
- Role and Mechanisms of Tumor-Associated Macrophages in Hematological Malignancies.Frontiers in oncology · 2022Review
- Therapeutic strategies for gastric cancer targeting immune cells: Future directions.Frontiers in immunology · 2022Review
- Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages.eLife · 2021Article
- Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges.Molecular pharmaceutics · 2021Review
- Novel approaches to target the microenvironment of bone metastasis.Nature reviews. Clinical oncology · 2021Review
- Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis.Cells · 2021Review
- Macrophage Plasticity and Function in the Lung Tumour Microenvironment Revealed in 3D Heterotypic Spheroid and Explant Models.Biomedicines · 2021Article
- The Mevalonate Pathway, a Metabolic Target in Cancer Therapy.Frontiers in oncology · 2021Review
- The Case of Medication-Related Osteonecrosis of the Jaw Addressed from a Pathogenic Point of View. Innovative Therapeutic Strategies: Focus on the Most Recent Discoveries on Oral Mesenchymal Stem Cell-Derived Exosomes.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process.Cancers · 2020Review
- Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.Frontiers in oncology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zoledronic acid (ZA) is a biphosphonate used for osteoporosis treatment and also proved to be effective to reduce the pain induced by bone metastases when used as adjuvant therapy in solid cancers. However, it has been recently proposed that ZA could have direct anti-tumour effects, although the molecular mechanism is unknown. We herein unravel a novel anti-tumour activity of ZA in prostate cancer (PCa), by targeting the pro-tumorigenic properties of both stromal and immune cells. Particularly, we demonstrate that ZA impairs PCa-induced M2-macrophages polarization, reducing their pro-invasive effect on tumour cells and their pro-angiogenic features. Crucially, ZA administration reverts cancer associated fibroblasts (CAFs) activation by targeting the mevalonate pathway and RhoA geranyl-geranylation, thereby impairing smooth muscle actin-α fibers organization, a prerequisite of fibroblast activation. Moreover, ZA prevents the M2 macrophages-mediated activation of normal fibroblast, highlighting the broad efficacy of this drug on tumour microenvironment. These results are confirmed in a metastatic xenograft PCa mouse model in which ZA-induced stromal normalization impairs cancer-stromal cells crosstalk, resulting in a significant reduction of primary tumour growth and metastases. Overall these findings reinforce the efficacy of ZA as a potential therapeutic approach to reduce cancer aggressiveness, by abrogating the supportive role of tumour microenvironment.
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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.