ReviewJournal of experimental & clinical cancer research : CR2019
RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives.
Review in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- Prognostic value of RANK signalling in breast cancer: a systematic review and meta-analysis.BMJ open · 2025Pooled it
- Long-term effect of neoadjuvant denosumab treatment in high-risk early breast cancer (GeparX).ESMO open · 2025Trial
- The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy.Breast cancer research : BCR · 2023Trial
- Osteogenic Marker Expression after SHED and PMMA-HA Scaffold Application in Alveolar Bone Defects.European journal of dentistry · 2026Article
- Article
- Article
- Tracking Bone Loss in GLP-1RA Therapy: The Potential of the Deoxypyridinoline Urine Test.Diagnostics (Basel, Switzerland) · 2026Article
- Mechanical Stimulation Drives Multicellular Synergy and Signaling Pathways in Developing Skeletal Tissues.Sports medicine (Auckland, N.Z.) · 2026Review
- TSP-1 interaction with RANK and OPG: implications for bone remodeling and osteolytic bone metastasis.Cell death & disease · 2026Article
- Recombinant Human Decorin Normalizes the Active Features of Breast Cancer-Associated Fibroblasts.Cells · 2026Article
- Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers ofWorld journal of oncology · 2026Review
- Distinctive features of cancer-associated fibroblasts expressing CD105, a novel biomarker for bone metastasis, in early-stage invasive ductal breast cancer.Frontiers in endocrinology · 2026Article
- A Crosstalk Between Periodontal Disease and Human Immunodeficiency Virus: Application of Artificial Intelligence and Machine Learning in Risk Assessment and Diagnosis-A Narrative Review.Dentistry journal · 2025Review
- Immune-Guided Bone Healing: The Role of Osteoimmunity in Tissue Engineering Approaches.International journal of molecular sciences · 2025Review
- Jianpi-Huogu Prescription Repairs Nontraumatic Osteonecrosis of the Femoral Head by Inhibiting NAMPT/STK11/HMGCR/ACAT1 Axis-Mediated Lipid Production.Journal of cellular and molecular medicine · 2025Article
- Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.Biomedicines · 2025Review
- Role of endosomal RANKL-LGR4 signaling during osteoclast differentiation.Journal of molecular medicine (Berlin, Germany) · 2025Article
- The Role of Osteoprotegerin in Breast Cancer: Genetic Variations, Tumorigenic Pathways, and Therapeutic Potential.Cancers · 2025Review
- Implications of Mineralization Biomarkers in Breast Cancer Outcomes Beyond Calcifications.International journal of molecular sciences · 2025Article
- Alternative Splicing: A Critical Regulator in Human Bone Biology and Tumor Progression.Research (Washington, D.C.) · 2025Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RANKL/RANK/OPG system consists of three essential signaling molecules: i) the receptor activator of nuclear factor (NF)-kB-ligand (RANKL), ii) the receptor activator of NF-kB (RANK), and iii) the soluble decoy receptor osteoprotegerin (OPG). Although this system is critical for the regulation of osteoclast differentiation/activation and calcium release from the skeleton, different studies have elucidated its specific role in mammary gland physiology and hormone-driven epithelial proliferation during pregnancy. Of note, several data suggest that progesterone induces mammary RANKL expression in mice and humans. In turn, RANKL controls cell proliferation in breast epithelium under physiological conditions typically associated with higher serum progesterone levels, such as luteal phase of the menstrual cycle and pregnancy. Hence, RANKL/RANK system can be regarded as a major downstream mediator of progesterone-driven mammary epithelial cells proliferation, potentially contributing to breast cancer initiation and progression. Expression of RANKL, RANK, and OPG has been detected in breast cancer cell lines and in human primary breast cancers. To date, dysregulation of RANKL/RANK/OPG system at the skeletal level has been widely documented in the context of metastatic bone disease. In fact, RANKL inhibition through the RANKL-blocking human monoclonal antibody denosumab represents a well-established therapeutic option to prevent skeletal-related events in metastatic bone disease and adjuvant therapy-induced bone loss in breast cancer. On the other hand, the exact role of OPG in breast tumorigenesis is still unclear. This review focuses on molecular mechanisms linking RANKL/RANK/OPG system to mammary tumorigenesis, highlighting pre-clinical and clinical evidence for the potential efficacy of RANKL inhibition as a prevention strategy and adjuvant therapy in breast cancer settings.
Indexed as
Identifiers
What OpenQuestion holds
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.