Trametinib Synergized With Abemaciclib to Inhibit Tumor Growth in Human Head and Neck Squamous Cell Carcinoma Cells

Background/aim: The cyclin-D-CDK4/6-RB pathway is often deregulated in head and neck squamous cell carcinoma (HNSCC), making it an attractive therapeutic target. However, previous studies showed that treatment with specific CDK4/6 inhibitors (CDK4/6Is) induced ROS generation and the activation of ERK phosphorylation in HNSCC, enabling Cancer cells escape from CDK4/6I-medicated cell cycle arrest. Here we aimed to explore the therapeutic effects of the combination of abemaciclib (CK4/6I) and trametinib (an ERK1/2 inhibitor) in preclinical models of HNSCCs.

Materials and methods: The activities of trametinib as a monotherapy and a combination therapy with abemaciclib in HNSCC cells and tumors were evaluated using cell viability assays, colony formation assays, and xenograft models, respectively.

Results: Trametinib enhanced the inhibitory effect of abemaciclib in HNSCC Cancer cells and xenografts, and the co-administration of abemaciclib and trametinib exhibited synergy in anti-tumor activities.

Conclusion: The combination of abemaciclib and trametinib potently repressed the growth of HNSCC cells and xenografts in a synergistic manner, thus being a potential therapeutic approach for HNSCC.

CDK4/6 inhibitors; ERK inhibitors; acquired resistance; head and neck squamous cell carcinoma; synergy.