{"entity":{"id":"rankl","kind":"target","name":"RANK ligand (RANKL)","aka":[],"tldr":"RANK ligand is the signal that tells bone-dissolving cells to get to work. Cancers in the bone hijack it; denosumab blocks it to prevent fractures and other bone complications.","summary":"Receptor activator of nuclear factor kappa-B ligand (TNFSF11) is produced by osteoblasts and stromal cells and binds RANK on osteoclast precursors, driving their maturation and bone resorption. Bone metastases and myeloma cells increase RANKL, feeding a vicious cycle of resorption and growth-factor release. Denosumab, a fully human anti-RANKL antibody, prevents skeletal-related events in bone metastases and myeloma (Xgeva) and treats giant cell tumour of bone and hypercalcaemia of malignancy; it is also an osteoporosis drug (Prolia). Osteonecrosis of the jaw and rebound fractures on discontinuation are the notable risks.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/RANKL","links":[{"label":"NCBI Gene TNFSF11","url":"https://www.ncbi.nlm.nih.gov/gene/8600"}],"tags":["bone"],"related":[],"cancers":["breast-hr-positive","prostate","multiple-myeloma"],"sections":[],"technologies":["bone-modifying-agents"],"targets":[],"drugs":["denosumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence is not a selection criterion: RANKL is produced mainly by osteoblasts and stromal cells and denosumab is given for bone metastases or myeloma regardless of tumour RANKL. No peer-reviewed series with a stated denominator was found for tumour-cell RANKL positivity in HR-positive breast cancer or multiple myeloma; the prostate row reflects a small primary-tumour series."],"symbol":"TNFSF11","role":[],"sources":[],"specificity":"immune-microenvironment","distribution":"few-types","specificityNote":"Immune or microenvironment target: the record's class is stroma. HPA TNFSF11: RNA tissue enhanced (liver 4 nTPM, lymphoid tissue 12 nTPM); blood lineage lineage enriched (NK-cells 10 nTPM); no normal tissue stained high; highest cancer staining skin cancer (1 of 10 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Prostate cancer, Breast cancer (all types), Multiple myeloma); approvals of single-target medicines aimed at it also list Lung cancer (all types), Sarcomas (soft tissue, bone, GIST), not counted; Open Targets associates it with 3 specific cancer types at or above 0.5 (bone giant cell tumor, giant cell tumor, plasma cell myeloma). (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas TNFSF11 tissue","url":"https://www.proteinatlas.org/ENSG00000120659-TNFSF11/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt O14788","url":"https://www.uniprot.org/uniprotkb/O14788/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000120659 associations","url":"https://platform.opentargets.org/target/ENSG00000120659/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11926","ensembl":"ENSG00000120659","uniprot":"O14788","entrez":"8600","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Anderson D.M. et al, Nature, 1997, \"A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9367155/","biology":"RANKL also functions in lymph node development and mammary gland biology; RANK signalling in breast epithelium has been linked to progestin-driven and BRCA1-associated tumorigenesis.","whereFound":["Bone metastases from breast, prostate and lung cancer","Multiple myeloma bone disease","Giant cell tumour of bone"],"targetClass":"stroma","prevalence":[{"cancerId":"prostate","pct":91,"measure":"IHC, RANKL in 10 of 11 primary prostate cancer specimens (heterogeneous staining)","source":"https://doi.org/10.1016/s0090-4295(00)01122-5","note":"Brown 2001 (Urology); 28 patients studied overall, all bone metastases were RANKL-immunoreactive and the fraction of positive tumour cells was higher in bone metastases than in primaries"}]},"route":"/targets/rankl/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"bone-modifying-agents","kind":"technology","name":"Bone-modifying agents (bisphosphonates, denosumab)","route":"/technologies/bone-modifying-agents/"}],"drug":[{"id":"denosumab","kind":"drug","name":"Denosumab","route":"/drugs/denosumab/"}]}}