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

  • Anticancer Res. 2025 Jun;45(6):2285-2295. doi: 10.21873/anticanres.17603.
Ernest Duah  1 ,  Ming Poi  1  2  3 ,  Junan Li  4  3  5
Affiliations
  • 1. Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
  • 2. Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
  • 3. The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, U.S.A.
  • 4. Division of Pharmacy Practice and Science, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.; [email protected].
  • 5. Division of Outcomes and Translational Sciences, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
PMID: 40425343 DOI: 10.21873/anticanres.17603
Abstract

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.

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