CXCR4 is the only functional chemokine receptor expressed on hematopoietic stem cells (HSC)
CXCL12 promotes:
CXCR4+ cell motility, stimulating cytoskeletal rearrangements (leading edge formation)
CXCR4+ cell homing to CXCL12-rich tissue by upregulating integrins and matrix metalloproteinases(MMPs)
CXCR4 / CXCL12 axis promotes tumor cell proliferation, angiogenesis, and evades the monitoring of the immune system for diffusion.
CXCR4 overexpression has been detected in > 48 cancer types.
Disrupt tumor-associated stromal interactions that confer tumor cell survival and drug resistance
Block paracrine growth and survival signals through activation of the CXCR4 / CXCL12 axis
Block CXCL12-mediated recruitment of proangiog enic, bone marrow-derived progenitor cells
Block tumor cell metastasis to distant CXCL12-rich stromal niches
Mobilize tumor cells from CXCL12-rich tissue to increase chemotherapeutic accessibility