ArticleBone research2019
Efficacy of an orally active small-molecule inhibitor of RANKL in bone metastasis.
Article in Bone research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
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Who cites it
29 citing papers in PubMed, 104 citations in OpenAlex.
- The interrelationship between prostate cancer and osteoporosis: new perspectives on shared molecular pathways and treatment strategies.International journal of surgery (London, England) · 2026Article
- Modeling and targeting the hostile physicochemical niche in bone metastasis: from experimental platforms to niche-directed therapy.Frontiers in cell and developmental biology · 2026Review
- A Novel RANKL/RANK Inhibitor IMB-R38 Inhibits Osteoporosis Through Regulating Bone Metabolism.International journal of molecular sciences · 2025Article
- Bone marrow endosteum in homeostasis and metastasis.Open biology · 2025Review
- RANKL Drives Bone Metastasis in Mammary Cancer: Protective Effects of Anti-Resorptive Treatments.International journal of molecular sciences · 2025Article
- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Insight into prostate cancer osteolytic metastasis by RelB coordination of IL-8 and S100A4.Clinical and translational medicine · 2024Article
- Review
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Bone serves as a transfer station for secondary dissemination of breast cancer.Bone research · 2023Review
- Muscle and Bone Defects in Metastatic Disease.Current osteoporosis reports · 2022Review
- RANKL biology.Bone · 2022Review
- Improved Characteristics of RANKL Immuno-PET Imaging Using Radiolabeled Antibody Fab Fragments.Pharmaceutics · 2022Article
- GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation.Bone research · 2022Article
- The role played by ailanthone in inhibiting bone metastasis of breast cancer by regulating tumor-bone microenvironment through the RANKL-dependent pathway.Frontiers in pharmacology · 2022Article
- Comprehensive circular RNA expression profile of lung adenocarcinoma with bone metastasis: Identification of potential biomarkers.Frontiers in genetics · 2022Article
- Development and Validation of Prognostic Nomogram for Elderly Breast Cancer: A Large-Cohort Retrospective Study.International journal of general medicine · 2022Article
- Osteosarcoma mechanobiology and therapeutic targets.British journal of pharmacology · 2022Review
- Poor bone matrix quality: What can be done about it?Current osteoporosis reports · 2021Review
- Dual effect of IL-7/IL-7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis.Immunology · 2021Article
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 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone is one of the preferred sites for the metastasis of malignant tumours, such as breast cancer, lung cancer and malignant melanoma. Tumour cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand (RANKL), which promotes osteoclast differentiation and activation. Tumour-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth, causing bone pain and hypercalcaemia. Furthermore, RANKL contributes to bone metastasis by acting as a chemoattractant to bone for tumour cells that express its receptor, RANK. Thus inhibition of the RANKL-RANK pathway is a promising treatment for bone metastasis, and a human monoclonal anti-RANKL antibody, denosumab, has been used in the clinic. However, orally available drugs targeting RANKL must be developed to increase the therapeutic benefits to patients. Here we report the efficacy of the small-molecule RANKL inhibitor AS2676293 in treating bone metastasis using mouse models. Oral administration of AS2676293 markedly inhibited bone metastasis of human breast cancer cells MDA-MB-231-5a-D-Luc2 as well as tumour-induced osteolysis. AS2676293 suppressed RANKL-mediated tumour migration in the transwell assay and inhibited bone metastasis of the murine cell line B16F10, which is known not to trigger osteoclast activation. Based on the results from this study, RANKL inhibition with a small-molecule compound constitutes a promising therapeutic strategy for treating bone metastasis by inhibiting both osteoclastic bone resorption and tumour migration to bone.
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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.