PRJNA474748
Cytokine sensitivity screening highlights BMP4 signaling as a therapeutic opportunity in ER+ breast cancer
Microenvironmental secreted factor screening revealed cytokines that modulate drug sensitivity in ER+ breast cancer cells. BMP4 was a top hit that is not normally expressed in ER+ breast cancer, and was found to enhance efficacy of anti-estrogens and CDK4/6i in anti-estrogen-sensitive and -resistant ER+ breast cancer cells. The anti-cancer effects of BMP4 were mediated by ALK3 and canonical BMP pathway signaling, leading to downstream p21 induction and cell cycle arrest. The clinical relevance of this phenotype was confirmed in analyses of 3 cohorts of patients with ER+ breast cancer, highlighting BMP4 pathway activation as a potential therapeutic opportunity in ER+ breast cancer.