Ceramide Nanoliposomes Synergize with Epidermal Growth Factor Receptor Inhibitors: Exploring a New Potential Therapy for Head and Neck Cancer Patients

Head and Neck Squamous Cell Carcinoma (HNSCC) is the 7th most common cancer worldwide. However, despite its prevalence, only one HNSCC-targeted therapy exists. Unfortunately, this therapy has only shown modest efficacy in patients; thus, the need to develop a more effective treatment arises. The ceramide nanoliposome (CNL) is a therapeutic currently in clinical trials for numerous cancers. Additionally, prior literature has thoroughly documented CNL’s ability to enhance the effectiveness of other drugs. The Epidermal Growth Factor Receptor (EGFR) is a particularly druggable target in HNSCC as it is overexpressed in 40-80% of tumors. From this, the potential for a combinatorial therapy between CNL and EGFR inhibitors presents itself. MTS cell viability assays confirmed the ineffectiveness of both Erlotinib and Gefitinib, two EGFR inhibitors that failed clinical trials in HNSCC. On the other hand, CNL was efficacious in killing eight different HNSCC cell lines. Most interestingly, when combined, CNL and both Erlotinib and Gefitinib induced greater HNSCC cell death than the additive effects of each drug alone, indicating pharmacological synergy. Flow cytometry was performed to validate this synergistic effect using a more precise cell viability dye. Western blotting identified cleavage of Poly (ADP-ribose) Polymerase (PARP), a protein responsible for DNA repair, independent of caspase-3 cleavage, a hallmark of apoptosis. This study characterizes a novel synergistic effect between CNL and Erlotinib or Gefitinib, gives insight into the mechanism behind this synergy, and provides evidence for such a combinatorial therapy to be developed for patients with HNSCC.