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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.
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.
In plain words · 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.
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.
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.
1 product aims at RANK ligand (RANKL): antibodies. The target is on the supporting tissue around the tumour, so drugs aim to breach the wall or use it as a beacon for radioligands and imaging.
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.)
Sources: Human Protein Atlas TNFSF11 tissue; UniProt O14788; Open Targets ENSG00000120659 associations
First described 1997. 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". Source.
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.
RNA: tissue enhanced (liver 4 nTPM, lymphoid tissue 12 nTPM), detected in some normal tissues. Blood: lineage enriched (NK-cells 10 nTPM).
No normal tissue stained high; medium in Bone marrow, Lymph node, Spleen, Tonsil.
RNA cancer enhanced: Pancreatic Adenocarcinoma 5 pTPM.
Medium only: endometrial cancer.
HPA TNFSF11 tissue · HPA TNFSF11 pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | 91% | IHC, RANKL in 10 of 11 primary prostate cancer specimens (heterogeneous staining) | 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 | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Denosumab is an injection under the skin that blocks the signal driving bone breakdown. As Xgeva it prevents fractures and other bone complications in people whose cancer has spread to bone or who have myeloma; as Prolia it treats osteoporosis, including bone loss caused by hormone therapy for breast and prostate cancer.
Query for this target: (TITLE:"RANK ligand" OR ABSTRACT:"RANK ligand" OR TITLE:"RANKL" OR ABSTRACT:"RANKL" OR TITLE:"TNFSF11" OR ABSTRACT:"TNFSF11") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about RANK ligand (RANKL), not a curated reading list.
Shares Bone-modifying agents (bisphosphonates, denosumab), Denosumab.
Shares Bone-modifying agents (bisphosphonates, denosumab), Denosumab, Multiple myeloma, HR-positive / HER2-negative breast cancer.
Shares Bone-modifying agents (bisphosphonates, denosumab), Denosumab, HR-positive / HER2-negative breast cancer.
Shares Bone-modifying agents (bisphosphonates, denosumab), Denosumab, Multiple myeloma, HR-positive / HER2-negative breast cancer.
Shares Bone-modifying agents (bisphosphonates, denosumab), Denosumab, Multiple myeloma, HR-positive / HER2-negative breast cancer.
Shares Bone-modifying agents (bisphosphonates, denosumab), Denosumab.
Shares Bone-modifying agents (bisphosphonates, denosumab), Denosumab, Multiple myeloma, HR-positive / HER2-negative breast cancer.
Shares Denosumab, Prostate cancer.