{"entity":{"id":"cxcr4","kind":"target","name":"CXCR4","aka":[],"tldr":"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.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/CXCR4","links":[{"label":"CXCR4 in WM (Blood 2014)","url":"https://doi.org/10.1182/blood-2014-01-550905"}],"tags":["gap-fill"],"related":[],"cancers":["waldenstrom","multiple-myeloma","aml"],"sections":[],"technologies":["autologous-stem-cell-transplant","radioligand-therapy"],"targets":[],"drugs":["mavorixafor","plerixafor"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-treon-blood"],"journals":[],"dependsOn":[],"notes":[],"symbol":"CXCR4","role":[],"sources":[],"specificity":"immune-microenvironment","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"Human Protein Atlas CXCR4 tissue","url":"https://www.proteinatlas.org/ENSG00000121966-CXCR4/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt P61073","url":"https://www.uniprot.org/uniprotkb/P61073/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000121966 associations","url":"https://platform.opentargets.org/target/ENSG00000121966/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:2561","ensembl":"ENSG00000121966","uniprot":"P61073","entrez":"7852","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8329116/","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).","whereFound":["Waldenström macroglobulinaemia (30-40% mutation)","Myeloma, lymphoma, AML (expression)","Breast, prostate and other solid tumours (metastatic homing)"],"targetClass":"other","prevalence":[{"cancerId":"waldenstrom","pct":"30-40","measure":"CXCR4 mutation","source":"https://doi.org/10.1182/blood-2014-01-550905"}]},"route":"/targets/cxcr4/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"waldenstrom","kind":"cancer","name":"Waldenström macroglobulinaemia","route":"/cancers/waldenstrom/"}],"technology":[{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"}],"drug":[{"id":"mavorixafor","kind":"drug","name":"Mavorixafor","route":"/drugs/mavorixafor/"},{"id":"plerixafor","kind":"drug","name":"Plerixafor","route":"/drugs/plerixafor/"}],"term":[{"id":"myd88-l265p","kind":"term","name":"MYD88 L265P and CXCR4 mutations","route":"/terms/myd88-l265p/"},{"id":"theranostics","kind":"term","name":"Theranostics","route":"/terms/theranostics/"}],"paper":[{"id":"paper-treon-blood","kind":"paper","name":"Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia","route":"/key-papers/paper-treon-blood/"},{"id":"paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013","kind":"paper","name":"Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer","route":"/key-papers/paper-feig-cxcl12-fap-cafs-t-cell-exclusion-pnas-2013/"}],"pathway":[{"id":"immune-desert-exclusion","kind":"pathway","name":"Cold tumours: immune deserts and exclusion","route":"/pathways/immune-desert-exclusion/"},{"id":"myeloid-suppression-axis","kind":"pathway","name":"Myeloid suppression: TAMs, MDSCs & don't-eat-me signals","route":"/pathways/myeloid-suppression-axis/"},{"id":"organ-tropism-seed-soil","kind":"pathway","name":"Organ tropism: seed and soil","route":"/pathways/organ-tropism-seed-soil/"},{"id":"pre-metastatic-niche","kind":"pathway","name":"The pre-metastatic niche","route":"/pathways/pre-metastatic-niche/"}],"company":[{"id":"biolinerx","kind":"company","name":"BioLineRx","route":"/companies/biolinerx/"}]}}