# RANK ligand (RANKL)

Source: https://onco.cc/targets/rankl/  
OnCo record `rankl` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Target
- Last checked: 2026-09-10
- Tags: bone
- Symbol: TNFSF11
- Class: stroma
- 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.
- Where found: Bone metastases from breast, prostate and lung cancer; Multiple myeloma bone disease; Giant cell tumour of bone

## 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/RANKL
- NCBI Gene TNFSF11: https://www.ncbi.nlm.nih.gov/gene/8600

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Bone-modifying agents (bisphosphonates, denosumab)](https://onco.cc/technologies/bone-modifying-agents/)
- drugs: [Denosumab](https://onco.cc/drugs/denosumab/)

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JSON: https://onco.cc/api/v1/entities/rankl.json