WEE1 inhibition delays resistance to CDK4/6 inhibitor and antiestrogen treatment in estrogen receptor-positive breast cancer.

ABSTRACT: Although endocrine therapies and Cdk4/6 inhibitors have produced significantly improved outcomes for patients with estrogen receptor positive (ER+) breast cancer, continuous application of these drugs often results in resistance. We hypothesized that cancer cells acquiring drug resistance might increase their dependency on negative regulators of the cell cycle. Therefore, we investigated the effect of inhibiting WEE1 on delaying the development of resistance to palbociclib and fulvestrant. We treated ER+ MCF7 breast cancer cells with palbociclib alternating with a combination of fulvestrant and a WEE1 inhibitor AZD1775 for 12 months. We found that the alternating treatment prevented the development of drug resistance to palbociclib and fulvestrant compared to monotherapies. Furthermore, we

SUBMITTER: He W 

PROVIDER: S-EPMC11429701 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature