This site is intended for
Healthcare Professionals only.

For Patients


CXCR4 pathway expressed on a tumor cell diagram

Chemokine (C-X-C motif) receptor 4 (CXCR4), a chemokine receptor expressed by immune and tumor cells, guides tumor-cell migration and is important for processes such as tumor metastasis. Inhibition of CXCR4 may impair these protumor effects.

  • CXCR4 is a G-protein–coupled receptor in the CXC chemokine receptor family found on the surface of immune cells, such as T cells1-3
    • The ligand for CXCR4 is (chemokine (C-X-C motif) ligand 12) CXCL12 or stromal cell-derived factor 1 (SDF-1), which is expressed by cells such as osteoblasts and endothelial cells5
    • Binding of CXCR4 to its ligand CXCL12 directs the migration and recruitment of immune cells,5,6 and is implicated in several biological processes such as immune response and cardiovascular development5
  • Preclinical data suggest that inhibition of the CXCR4 pathway may have a dual effect, as it impairs tumor-cell migration and blocks tumor growth.10 It also increases mobilization of leukocytes and leukemic blasts into the peripheral circulation, resulting in significant antileukemic activity11
    • CXCR4 may also promote the accumulation of cytotoxic
      T cells

Get I-O Resources

Order or download
educational tools for your
patients and practice

See all resources

Clinical Trials

Learn more about our
current clinical trials

Learn more


1. Xu C, Zhao H, Chen H, Yao Q. CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther. 2015;9:4953-4964. 2. Lee B, Sharron M, Montaner LJ, et al. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci U S A. 1999;96(9):5215-5220. 3. Loetscher M, Geiser T, O’Reilly T, et al. Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem. 1994;269(1):232-237. 4. Helbig G, Christopherson KW II, Bhat-Nakshatri P, et al. NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem. 2003;278(24):21631-21638. 5. Cheng M, Qin G. Progenitor cell mobilization and recruitment: SDF-1, CXCR4, α4-integrin, and c-kit. Prog Mol Biol Transl Sci. 2012;111:243-264. 6. Oberlin E, Amara A, Bachelerie F, et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature. 1996;382(6594):833-835. 7. Sun X, Cheng G, Hao M, et al. CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression. Cancer Metastasis Rev. 2010;29(4):709-722. 8. Sehgal A, Keener C, Boynton AL, et al. CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells. J Surg Oncol. 1998;69(2):99-104. 9. Chen Y, Stamatoyannopoulos G, Song C-Z. Down-regulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro. Cancer Res. 2003;63(16):4801-4804. 10. Righi E, Kashiwagi S, Yuan J, et al. CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer. Cancer Res. 2011;71(16):5522-5534. 11. Kuhne MR, Mulvey T, Belanger B, et al. BMS-936564/MDX-1338: a fully human anti-CXCR4 antibody induces apoptosis in vitro and shows antitumor activity in vivo in hematologic malignancies. Clin Cancer Res. 2013;19(2):357-366.