Cytokine sensitivity screening highlights BMP4 pathway signaling as a therapeutic opportunity in ER⁺ breast cancer.

ABSTRACT: 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). BM

SUBMITTER: Shee K 

PROVIDER: S-EPMC6338642 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature