biostudies-literatureShee KBLRD VANorris Cotton Cancer CenterNational Cancer InstituteNCI NIH HHSNational Institutes of Health1644-1657https://www.ebi.ac.uk/biostudies/studies/S-EPMC6338642biostudies-literatureUnknown33(2)Despite the success of approved systemic therapies for estrogen receptor α (ER)-positive breast cancer, drug resistance remains common. We hypothesized that secreted factors from the human tumor microenvironment could modulate drug resistance. We previously screened a library of 297 recombinant-secreted microenvironmental proteins for the ability to confer resistance to the anti-estrogen fulvestrant in 2 ER⁺ breast cancer cell lines. Herein, we considered whether factors that enhanced drug sensitivity could be repurposed as therapeutics and provide leads for drug development. Screening data revealed bone morphogenic protein (BMP)4 as a factor that inhibited cell growth and synergized with approved anti-estrogens and cyclin-dependent kinase 4/6 inhibitors (CDK4/6_i). BMFASEB journal : official publication of the Federation of American Societies for Experimental BiologyCytokine sensitivity screening highlights BMP4 pathway signaling as a therapeutic opportunity in ER⁺ breast cancer.PMC6338642R01 CA211869P30CA023108IK2 BX002929F30CA216966P30 CA023108R01CA211869F30 CA216966R01 CA200994Varn FSCheng CHoog JJiang ATraphagen NAMa CXStraussman RMiller TWShee KLiu SOwens PGolub TRfalseCytokine sensitivity screening highlights BMP4 pathway signaling as a therapeutic opportunity in ER⁺ breast cancer.Despite the success of approved systemic therapies for estrogen receptor α (ER)-positive breast cancer, drug resistance remains common. We hypothesized that secreted factors from the human tumor microenvironment could modulate drug resistance. We previously screened a library of 297 recombinant-secreted microenvironmental proteins for the ability to confer resistance to the anti-estrogen fulvestrant in 2 ER⁺ breast cancer cell lines. Herein, we considered whether factors that enhanced drug sensitivity could be repurposed as therapeutics and provide leads for drug development. Screening data revealed bone morphogenic protein (BMP)4 as a factor that inhibited cell growth and synergized with approved anti-estrogens and cyclin-dependent kinase 4/6 inhibitors (CDK4/6_i). BM2019-01-01T00:00:00Z2019 Feb2026-05-06T22:43:22.865Z2020-05-22T15:26:26ZS-EPMC63386423016100110.1096/fj.201801241R10.1096/fj.201801241r