Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models.

ABSTRACT: Resistance to therapy remains a major obstacle in cancer management. Although treatment with hormone and CDK4/6 inhibitors is successful in luminal breast cancer, resistance to these treatments is frequent, highlighting the need for novel therapeutic strategies to delay disease progression and improve patient survival. Here, we assessed the mechanisms of acquired resistance using T47D and MCF-7 tamoxifen- and palbociclib-resistant cell-line variants in culture and as xenografts, and patient-derived cells (PDCs) obtained from sensitive or resistant patient-derived xenografts (PDXs). In these models, we analyzed the effect of specific kinase inhibitors on survival, signaling and cellular aggressiveness. Our results revealed that mTOR inhibition is more effective than PI3K inhibition in overc

SUBMITTER: Rodriguez MJ 

PROVIDER: S-EPMC9932145 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature