Inhibiting BACE1 for NSCLC brain metastasis

Inhibiting the amyloid precursor-cleaving protein BACE1 could help treat NSCLC cancer brain metastasis by preventing its cleavage of wild-type EGFR, which induces ligand-independent activation of MEK/ERK signaling that drives tumor growth and migration.

In a patient-derived orthotopic xenograft mouse model of metastatic NSCLC, a genome-wide CRISPR activation screen targeting 18,885 genes identified BACE1 as the gene whose activating guide RNA was the most enriched in the brain relative to the lung. ...