Targeting GDNF and VLA-6 pathways for breast cancer leptomeninges metastasis

Inhibiting the macrophage-secreted neuronal survival factor GDNF, its tumor-expressed receptor NCAM, or the laminin receptor VLA-6 expressed by tumors, could help prevent leptomeningeal disease in breast cancer by decreasing breast cancer cell migration from the bone marrow to the survival-promoting environment in the leptomeninges.

In tumor samples from breast cancer patients, NCAM protein expression was associated with meningeal metastasis, and VLA-6 protein expression was higher in meningeal metastases than in primary tumors, bone marrow metastases, or brain parenchymal metastases. ...