CDK4/6 INHIBITORS AS NOVEL THERAPY IN NASOPHARYNGEAL CARCINOMA

Abstract

Nasopharyngeal carcinoma (NPC) is among the top 10 most common cancers in male in Singapore and there is currently no approved targeted therapy. This study demonstrated the role of CDk4/6-CyclinD1 pathway in patient samples and cell line models. Pharmacological inhibition of CDK4/6-CyclinD1 pathway by Abemacicib effectively resulted in growth inhibition in both cell lines and xenograft model. Global proteomic analysis and flow cytometry analysis have demonstrated that Abemaciclib majorly exerts its growth inhibition effect in NPC through G1 cell cycle arrest and also through other non-canonical pathways. High throughput screening with targeted therapy drug library identified EGFR inhibitors as one of the potential class of drug that can enhance the efficacy of Abemaciclib in NPC cell lines. In summary, this study demonstrates that G1/S transition pathway is an important oncogenic pathway in NPC and is a potential therapeutic target for this deadly disease which currently lacks targeted therapy.