GM-CSF - an oncogenic driver of HER2+ breast leptomeningeal metastasis.

and OPCs, cultured alone or with Lepto cells, revealed TPP1 as the regulator of GM-CSF; it mediates GM-CSF proteolytic degradation and suppresses signaling, thereby decreasing Lepto cell viability and tumor progression. Remarkably, combinatorial treatment of anti-GM-CSF antibody with a pan-Aurora kinase inhibitor (CCT137690) synergistically halts GM-CSF signaling and HER2+ LC growth in vitro and in vivo . Our work has demonstrated neural niche-specific crosstalk between HER2+ LC tumors and OPCs and established the efficacy of intrathecal administration of TPP1 protease, anti-GM-CSF antibodies, and pan-Aurora kinase inhibitors in combating HER2+ LC (Figure 1). This may offer a targetable axis to treat HER2+ LC in the clinics.