A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells.

ABSTRACT: Resistance to anti-estrogen therapy is an unsolved clinical challenge in successfully treating ER+ breast cancer patients. Recent studies have demonstrated the role of non-genetic (i.e. phenotypic) adaptations in tolerating drug treatments; however, the mechanisms and dynamics of such non-genetic adaptation remain elusive. Here, we investigate coupled dynamics of epithelial-mesenchymal transition (EMT) in breast cancer cells and emergence of reversible drug resistance. Our mechanism-based model for underlying regulatory network reveals that these two axes can drive one another, thus enabling non-genetic heterogeneity in a cell population by allowing for six co-existing phenotypes: epithelial-sensitive, mesenchymal-resistant, hybrid E/M-sensitive, hybrid E/M-resistant, mesenchymal-sensitive

SUBMITTER: Sahoo S 

PROVIDER: S-EPMC8271219 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature