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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.
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.
In plain words · 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.
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.
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).
2 products aim at CXCR4: small molecules. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
Immune or microenvironment target: its medicines act on immune, stromal or bone cells rather than on the tumour cell (drug mechanisms in the corpus). HPA CXCR4: RNA tissue enhanced (bone marrow 1,175 nTPM, lymphoid tissue 523 nTPM); no normal tissue stained high. Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Multiple myeloma, Leukaemia); Open Targets associates it with 3 specific cancer types at or above 0.5 (plasma cell myeloma, non-Hodgkin lymphoma, lymphoma). (Rule 1 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas CXCR4 tissue; UniProt P61073; Open Targets ENSG00000121966 associations
First described 1993. Earliest sequence paper UniProt cites for the protein: Herzog et al, DNA Cell Biol, 1993, "Molecular cloning, characterization, and localization of the human homolog to the reported bovine NPY Y3 receptor: lack of NPY binding and activation". Source.
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).
RNA: tissue enhanced (bone marrow 1,175 nTPM, lymphoid tissue 523 nTPM), detected in all normal tissues.
No normal tissue stained high.
No cancer sample stained medium or high.
HPA CXCR4 tissue · HPA CXCR4 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 |
|---|---|---|---|---|
| Waldenström macroglobulinaemia | 30-40% | CXCR4 mutation | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Mavorixafor is a once-daily tablet that blocks CXCR4, a receptor that traps white cells in the bone marrow. It is approved for the rare immunodeficiency WHIM syndrome and is being tested in Waldenström macroglobulinaemia, where CXCR4 mutations blunt the response to ibrutinib.
Plerixafor (Mozobil) is an injection given with G-CSF to flush stem cells out of the bone marrow into the blood so that enough can be collected for an autologous transplant in myeloma or lymphoma.
One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
The mechanistic account of T-cell exclusion that all later combination immunotherapy trials in pancreatic cancer cite, and the origin of CXCR4 inhibitor combinations.
Query for this target: (TITLE:"CXCR4" OR ABSTRACT:"CXCR4") 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 CXCR4, not a curated reading list.
Shares BioLineRx, Plerixafor, Multiple myeloma.
Shares BioLineRx, Multiple myeloma.
Shares Plerixafor, Multiple myeloma.
Shares Plerixafor, Multiple myeloma.
Shares Autologous stem cell transplant (high-dose therapy), Acute myeloid leukaemia, Multiple myeloma.
Shares Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer, Myeloid suppression: TAMs, MDSCs & don't-eat-me signals, Cold tumours: immune deserts and exclusion.
Shares The pre-metastatic niche, Myeloid suppression: TAMs, MDSCs & don't-eat-me signals.