# CXCR4

Source: https://onco.cc/targets/cxcr4/  
OnCo record `cxcr4` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A chemokine receptor that anchors blood cells in the marrow and helps cancer cells home to it; mutated in a third of Waldenström patients and targeted by plerixafor for stem-cell mobilisation.

## Summary

CXCR4 binds CXCL12 (SDF-1) to retain haematopoietic stem cells in the marrow niche and guides metastasis of solid tumours to bone. Plerixafor (2008) blocks it to mobilise stem cells for autologous transplant; motixafortide (2023) does the same in myeloma. WHIM-like CXCR4 mutations in ~30-40% of Waldenström macroglobulinaemia slow BTK-inhibitor response; mavorixafor is in trials. CXCR4 is also imaged with Ga-68 pentixafor and treated with Lu-177 pentixather in marginal zone lymphoma and myeloma (theranostic, experimental). Balixafortide and ulocuplumab failed in solid tumours.

## Fields

- Kind: Target
- Last checked: 2026-09-08
- Tags: gap-fill
- Symbol: CXCR4
- Class: other
- Biology: G-protein-coupled receptor; CXCL12 binding activates Gαi, PI3K/AKT and MAPK, promoting chemotaxis, survival and retention in stromal niches; truncating C-terminal mutations impair receptor internalisation (WHIM syndrome).
- Where found: Waldenström macroglobulinaemia (30-40% mutation); Myeloma, lymphoma, AML (expression); Breast, prostate and other solid tumours (metastatic homing)

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/CXCR4
- CXCR4 in WM (Blood 2014): https://doi.org/10.1182/blood-2014-01-550905

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Waldenström macroglobulinaemia](https://onco.cc/cancers/waldenstrom/)
- technologies: [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [Radioligand therapy (beta emitters)](https://onco.cc/technologies/radioligand-therapy/)
- drugs: [Mavorixafor](https://onco.cc/drugs/mavorixafor/), [Plerixafor](https://onco.cc/drugs/plerixafor/)
- terms: [MYD88 L265P and CXCR4 mutations](https://onco.cc/terms/myd88-l265p/), [Theranostics](https://onco.cc/terms/theranostics/)
- key papers: [Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia](https://onco.cc/key-papers/paper-treon-blood/), [Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer](https://onco.cc/key-papers/paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013/)
- pathways: [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [Myeloid suppression: TAMs, MDSCs & don't-eat-me signals](https://onco.cc/pathways/myeloid-suppression-axis/), [Organ tropism: seed and soil](https://onco.cc/pathways/organ-tropism-seed-soil/), [The pre-metastatic niche](https://onco.cc/pathways/pre-metastatic-niche/)
- companies: [BioLineRx](https://onco.cc/companies/biolinerx/)

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JSON: https://onco.cc/api/v1/entities/cxcr4.json