Therapeutics: E selectin (SELE; CD62E); CXC chemokine receptor 4 (CXCR4; NPY3R)

Patient sample and mouse studies suggest inhibiting SELE and/or CXCR4 could help prevent bone metastases of breast cancer. Levels of CXCR4 and several SELE ligands were higher in primary tumors from breast cancer patients who later showed bone marrow metastases than in tumors from breast cancer patients who did not. In a xenograft mouse model of breast cancer, the SELE inhibitor GMI-1271 decreased entry of circulating cancer stem cells into the bone marrow compared with vehicle, whereas the CXCR4 antagonist Mozobil plerixafor increased exit of adherent cancer stem cells from the bone marrow compared with vehicle. Next steps include testing a dual chemokine CXC motif ligand 12 (CXCL12; SDF-1)/SELE inhibitor in mouse models of breast cancer that metastasizes to the bone marrow.

Sanofi markets the synthetic CXCR4 antagonist Mozobil to treat multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) and has the compound in Phase I testing for acute myelogenous leukemia (AML)...