Abstract 4610: Dual inhibition of CDK4/6 and IL-6 pathways as a novel therapeutic approach for triple-negative breast cancer cells

Abstract Triplenegative breast cancer (TNBC) is highly aggressive and associated with poor clinical outcomes. TNBC stands as a major cause of death among breast cancer patients and offers only a few therapeutic options. Abemaciclib, a cyclin dependent kinase 4/6 (CDK4/6) inhibitor, has received FDA approval for use in hormone receptor-positive, HER2-negative, and metastatic breast cancers. However, acquired resistance to CDK4/6 inhibitors in treating TNBC is becoming an increasing concern. Our recent results indicated that CDK4/6 inhibitors can induce IL-6 levels in TNBC cells as a potential resistance mechanism by augment IL-6 signaling axis, and that targeting IL-6 signaling can sensitize TNBC cells to CDK4/6 inhibitor therapy. In this study, combination of Abemaciclib with an IL-6/GP130 inhibitor (bazedoxifene) was tested in TNBC cells. We examined the effect of the combination on cell viability, cell migration, and invasion of human and mouse TNBC cell lines. Our data demonstrated that the bazedoxifene and abemaciclib combination treatment synergistically inhibited TNBC cell viability, cell migration, and invasion in vitro. These results support dual inhibition of CDK4/6 and IL-6 as a novel therapeutic approach for TNBC. Citation Format: Kailey Caroland, Changyou Shi, Hui-Wen Lo, Jiayuh Lin. Dual inhibition of CDK4/6 and IL-6 pathways as a novel therapeutic approach for triple-negative breast cancer cells abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 4610.