BioCentury

WWTR1-AXL-ABL2 axis inhibition for brain metastases in lung cancer

January 29, 2020 11:17 PM UTC

INDICATION: Lung cancer

Blocking a signaling loop comprised of the transcription factor WWTR1 and the tyrosine kinases AXL and ABL2 could treat metastatic lung cancer. AXL and ABL2 signal between each other, and ABL2 activates WWTR1. In patients, high levels of WWTR1, AXL and ABL2 were associated with reduced overall survival (OS) and progression-free survival. In a xenograft mouse model of lung cancers, shRNAs against AXL or ABL2 increased brain metastasis-free survival and OS; and shRNAs against WWTR1 or AXL reduced disease burden in the brain. Asciminib, an inhibitor of BCR-ABL tyrosine kinase (BCR-ABL), also increased OS in the mice...