ReviewNature reviews. Clinical oncology2018
Roles of the RANKL-RANK axis in antitumour immunity - implications for therapy.
Review in Nature reviews. Clinical oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Interleukin-17A mRNA Expression is Associated with the Prognosis of Patients with Colorectal Cancer: A Pooled Meta-Analysis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Pooled it
- Denosumab as an immune modulator in HER2-negative early breast cancer: results of the window-of-opportunity D-BIOMARK clinical trial.Breast cancer research : BCR · 2025Trial
- Dissociated skeletal response to first-line immunotherapy in synchronous bone metastatic non-small cell lung cancer patients: Clinical profiles and survival benefit of denosumab adjunction.Journal of bone oncology · 2026Article
- Efficacy and safety of combined RANKL and PD-1 inhibitors in bone metastases: a retrospective study.Translational cancer research · 2026Article
- The osteoporotic niche as a metabolic sanctuary for breast cancer dormancy and reactivation: A mechanistic perspective.iScience · 2026Review
- Uncovering the Intricate and Heterogeneous Cellular Microenvironment of Cutaneous Melanoma.Medicina (Kaunas, Lithuania) · 2026Review
- Impact of bone-targeting agents on the clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab: a sub-analysis of the Meet-URO 15 study.Frontiers in oncology · 2026Article
- Review
- Brain-Bone Axis in Physiological and Pathological Conditions.International journal of molecular sciences · 2025Review
- RANKL/PD-1 dual blockade demonstrates survival benefit for patients with advanced lung adenocarcinoma harboring KRAS mutations.Cell reports. Medicine · 2025Article
- Ferulic Acid Alleviates Inflammation and Promotes Osteogenic Differentiation in Periodontitis by Inhibiting NF-Stem cells international · 2025Article
- The theoretical impact of AI-based quality evaluation of short-video health information on public cognition and treatment adherence: a case study of denosumab combined with PD-1/PD-L1 therapy for lung cancer bone metastasis.Frontiers in public health · 2025Article
- RANK/RANKL Signaling Pathway in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- Synergistic effect between denosumab and immune checkpoint inhibitors (ICI)? A retrospective study of 268 patients with ICI and bone metastases.Journal of bone oncology · 2024Article
- RANK and RANKL Expression in Tumors of Patients with Early Breast Cancer.Geburtshilfe und Frauenheilkunde · 2024Article
- Cytokines in gingivitis and periodontitis: from pathogenesis to therapeutic targets.Frontiers in immunology · 2024Review
- Downregulation of osteoprotegerin in colorectal cancer cells promotes liver metastasis via activating tumor-associated macrophage.Scientific reports · 2023Article
- Repurposing drugs for solid tumor treatment: focus on immune checkpoint inhibitors.Cancer biology & medicine · 2023Review
- Dendritic cells as shepherds of T cell immunity in cancer.Immunity · 2023Review
- OncoTheradJournal of cancer research and clinical oncology · 2023Article
8 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
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recognizing that the transformative effects of immunotherapy are currently limited to a minority of patients with cancer, research efforts are increasingly focused on expanding and enhancing clinical responses by combining immunotherapies; the repurposing of existing drugs is an attractive approach, given their well-characterized safety and pharmacokinetic profiles. Receptor activator of nuclear factor-κB (RANK) and the RANK ligand (RANKL) were initially described in the context of T cell-dendritic cell interactions; however, the discovery of an obligate role of RANK signalling in osteoclastogenesis led to the development of the anti-RANKL antibody denosumab for antiresorptive indications, including bone metastases. Randomized clinical trials and post-marketing surveillance studies have established the acceptable safety profile of denosumab. More recently, several case reports involving patients with advanced-stage melanoma have described remarkable responses following concurrent treatment with denosumab and immune-checkpoint inhibitors. Randomized trials assessing similar combinations in patients with melanoma or renal cell carcinoma are now underway. Herein, we discuss the hallmark clinical trials of denosumab in light of possible immunological effects of this agent. We highlight the role of immune cells as sources of RANK and RANKL in the tumour microenvironment and review data on RANKL inhibition in mouse models of cancer. Finally, we describe hypothetical immune-related mechanisms of action, which could be assessed in clinical trials of immune-checkpoint inhibitors and denosumab in patients with cancer.
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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.