Abstract
Efficacy of Cetuximab and 4-PBA Combination Therapy in Human Oral Squamous Cell Carcinoma Cells
Highlights
Cetuximab is a powerful anti-neoplastic agent that can inhibit cell growth in oral squamous cell carcinomas (OSCCs)
To investigate the effect of histone deacetylase inhibitors (HDACi) in OSCC cells, B88 and KOSC-2 cells were treated with cetuximab, HDACi (200nM trichostatin A, 5mM 4-phenyl butyric acid (4-PBA), 60μM splitomicin, 50nM apicidin, 1mM valproic acid), or the combination of cetuximab and HDACi
We demonstrated that cetuximab with 4-PBA induced histone acetylation and/or ER stress responses in OSCC cells, providing novel insights into the 4-PBA-mediated enhancement of antitumor activity by cetuximab
Summary
Cetuximab is a powerful anti-neoplastic agent that can inhibit cell growth in oral squamous cell carcinomas (OSCCs). Oral squamous cell carcinoma (OSCC) is a cancer originating from the oral mucosal epithelium that accounts for more than 90% of malignant tumors of the oral cavity and considerably influences the quality of life. EGFR is an important therapeutic target and prognostic factor for OSCC treatment. Treatment with the monoclonal antibody cetuximab exerts beneficial clinical effects. Cetuximab inhibits the binding of EGFR to its ligands and blocks the downstream signal transduction pathways, leading to inhibition of proliferation and apoptosis induction in tumor cells [4]. RAS somatic mutations are negative predictors of the clinical efficacy of anti-EGFR antibodies. Routine screening for mutations in K-RAS is used in colorectal cancer for patient selection prior to treatment [5, 6]. In OSCC, primary RAS mutations are rare and the importance of the mutations remain unclear [7, 8]
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