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

Abstract

Triple-negative 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/advanced 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, and increased IL-6 signaling could potentially compromise the efficacy of CDK4/6 inhibitors. In this study, abemaciclib was combined with an IL-6/GP130 inhibitor (bazedoxifene). We tested the effect of the combination on cell viability, migration, and invasion of human and mouse TNBC cells. Our data demonstrated that the bazedoxifene and abemaciclib combination synergistically inhibited TNBC cell viability, migration, and invasion in vitro. These results support dual inhibition of CDK4/6 and IL-6 as a novel therapeutic approach for TNBC.