CXCR4
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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).
- 3 · How drugs use it
1 product aims at CXCR4: imaging agents. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
External identifiers
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).
- Waldenström macroglobulinaemia (30-40% mutation)
- Myeloma, lymphoma, AML (expression)
- Breast, prostate and other solid tumours (metastatic homing)
An experimental PET tracer that looks for a specific docking protein (CXCR4) that some blood cancers and a minority of solid tumours carry in excess. It is a research tool, not an approved scan.
Latest papers
topQuery for this target: (TITLE:"CXCR4" OR ABSTRACT:"CXCR4") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR 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.
Similar pages
not linked directly; found by shared links- CompanyAlpha-9 Oncology
Shares Gallium-68, Radioligand therapy (beta emitters), Lutetium-177.
- Key paperRadiopharmaceutical therapy in cancer: clinical advances and challenges
Shares Theranostics, Radioligand therapy (beta emitters), Lutetium-177.
- PersonJohannes Czernin
Shares Gallium-68, Radioligand therapy (beta emitters), Lutetium-177.
- TrialA Study to Assess Safety, Tolerability and Imaging Characteristics of [68Ga]Ga-DPI-4452 and to Assess Safety, Tolerability, and Efficacy of [177Lu]Lu-DPI-4452 in Participants With Unresectable Locally Advanced or Metastatic Solid Tumors
Shares Gallium-68, Lutetium-177.
- AgentLocametz (kit for Ga-68 gozetotide)
Shares Theranostics, Gallium-68, Radioligand therapy (beta emitters), Lutetium-177.
- PersonPeter Bartenstein
Shares Gallium-68, Radioligand therapy (beta emitters), Lutetium-177.
- InstitutionErasmus MC Cancer Institute
Shares Theranostics, Radioligand therapy (beta emitters), Lutetium-177.
- CompanyClarity Pharmaceuticals
Shares Theranostics, Gallium-68, Radioligand therapy (beta emitters).