ReviewBoneKEy reports2014
Targeting RANKL in metastasis.
Review in BoneKEy reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis.The Cochrane database of systematic reviews · 2020Pooled it
- Efficacy and safety of JMT103 in patients with bone metastases from solid tumors: A randomized Phase Ib clinical trial.International journal of cancer · 2025Trial
- RANK/RANKL Signaling Pathway in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- Cellular signatures in human blood track bone mineral density in postmenopausal women.JCI insight · 2024Article
- Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases.Genes and immunity · 2024Review
- RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.Cell death & disease · 2024Article
- [Giant cell tumor of bone-an update].Pathologie (Heidelberg, Germany) · 2023Review
- Metastatic Lung Cancer to the Head and Neck: A Clinico-Pathological Study on 21 Cases with Narrative Review of the Literature.Journal of clinical medicine · 2023Article
- Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials.Frontiers in oncology · 2023Review
- Glutathione peroxidase 8 expression on cancer cells and cancer-associated fibroblasts facilitates lung cancer metastasis.MedComm · 2022Article
- Bone metastases in non-small cell lung cancer: a narrative review.Journal of thoracic disease · 2022Review
- Review
- What are the efficacy and safety of bisphosphonates and RANK-ligand-inhibitors for men with prostate cancer and bone metastases? - A Cochrane Review summary with commentary.Journal of musculoskeletal & neuronal interactions · 2021Article
- Deciphering molecular mechanisms of metastasis: novel insights into targets and therapeutics.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Article
- Biomechanical Properties of Metastatically Involved Osteolytic Bone.Current osteoporosis reports · 2020Review
- Primary tumor and metastasis-sectioning the different steps of the metastatic cascade.Translational lung cancer research · 2020Review
- RANKL triggers resistance to TRAIL-induced cell death in oral squamous cell carcinoma.Journal of cellular physiology · 2020Article
- Molecular mechanisms and clinical management of cancer bone metastasis.Bone research · 2020Review
- RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives.Journal of experimental & clinical cancer research : CR · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acting through its cognate receptor, receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) is an essential mediator of osteoclast function and survival. Preclinical data have now firmly established that blockade of tumor-induced osteoclastogenesis by RANKL inhibition will not only protect against bone destruction but will also inhibit the progression of established bone metastases and delay the formation of de novo bone metastases in cancer models. In patients with bone metastases, skeletal complications are driven by increased osteoclastic activity and may result in pathological fractures, spinal cord compression and the need for radiotherapy to the bone or orthopedic surgery (collectively known as skeletal-related events (SREs)). Denosumab, a fully human monoclonal antibody against RANKL, has been demonstrated to prevent or delay SREs in patients with solid tumors that have metastasized to bone. In addition to its central role in tumor-induced osteolysis, bone destruction and skeletal tumor progression, there is emerging evidence for direct pro-metastatic effects of RANKL, independent of osteoclasts. For example, RANKL also stimulates metastasis via activity on RANK-expressing cancer cells, resulting in increased invasion and migration. Pharmacological inhibition of RANKL may also reduce bone and lung metastasis through blockade of the direct action of RANKL on metastatic cells. This review describes these distinct but potentially overlapping mechanisms by which RANKL may promote metastases.
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.