ONC201/TIC10 enhances durability of mTOR inhibitor everolimus in metastatic ER+ breast cancer.

ABSTRACT: The mTOR inhibitor, everolimus, is an important clinical management component of metastatic ER+ breast cancer (BC). However, most patients develop resistance and progress on therapy, highlighting the need to discover strategies that increase mTOR inhibitor effectiveness. We developed ER+ BC cell lines, sensitive or resistant to everolimus, and discovered that combination treatment of ONC201/TIC10 with everolimus inhibited cell growth in 2D/3D in vitro studies. We confirmed increased therapeutic response in primary patient cells progressing on everolimus, supporting clinical relevance. We show that ONC201/TIC10 mechanism in metastatic ER+ BC cells involves oxidative phosphorylation inhibition and stress response activation. Transcriptomic analysis in everolimus resistant breast patient tumo

SUBMITTER: Farmaki E 

PROVIDER: S-EPMC10541180 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature