Molecular Analysis of Breast Cancer Metastasis to the Brain

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The lab completed preclinical experiments credentialling a CSF-1R inhibitor for triple-negative brain metastases of breast cancer. Using the Novatris BLZ945 compound, we found significant activity in both prevention of brain metastasis formation and treatment of established lesions in two in vivo models of triple-negative breast cancer brain metastasis. Both microglia and activated astrocytes were inhibited by treatment. Normal microglia in uninvolved brain were only inhibited by ~30%, suggesting that adverse events to the normal brain may be minimized. Three animal models of leptomeningeal metastasis have been developed based on intraventricular injection. The first model, HER2+, is being prepared for publication. We report that this model colonizes the leptomeninges of the brain and spinal column. Trastuzumab deruxtecan showed efficacy in this model.