Co-treatment with vactosertib, a novel, orally bioavailable activin receptor-like kinase 5 inhibitor, suppresses radiotherapy-induced epithelial-to-mesenchymal transition, cancer cell stemness, and lung metastasis of breast cancer

Abstract

Acquired metastasis and invasion of cancer cells during radiotherapy are in part due to induction of epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) properties, which are mediated by TGF-β signaling. Here we evaluated the anti-metastatic therapeutic potential of vactosertib, an orally bioavailable TGF-β type I receptor (activin receptor-like kinase 5, ALK5) inhibitor, via suppression of radiation-induced EMT and CSC properties, oxidative stress generation, and breast to lung metastasis in a breast cancer mouse model and breast cancer cell lines.

Keywords

• vactosertib
• transforming growth factor-β (tgf-β)
• radiotherapy
• epithelial-to-mesenchymal transition
• cancer stem cell
• breast cancer