Protein Farnesylation on Nasopharyngeal Carcinoma, Molecular Background and Its Potential as a Therapeutic Target

SIMPLE SUMMARY: Nasopharyngeal carcinoma is distinguished from other head and neck carcinomas by the association of its carcinogenesis with the Epstein–Barr virus. It is highly metastatic, and a novel therapeutic modality for metastatic nasopharyngeal carcinoma is keenly awaited. Protein farnesylation is a C-terminal lipid modification of proteins and was initially investigated as a key process in activating the RAS oncoprotein through its association with the cellular membrane structure. Since then, more and more evidence has accumulated to indicate that proteins other than RAS are also farnesylated and have significant roles in carcinogenesis. This review delineates molecular pathogenesis through protein farnesylation in the context of nasopharyngeal carcinoma and discusses the potential of farnesylation as a therapeutic target. ABSTRACT: Nasopharyngeal carcinoma (NPC) is one of the Epstein–Barr virus (EBV)-associated malignancies. NPC is highly metastatic compared to other head and neck carcinomas, and evidence has shown that the metastatic features of NPC are involved in EBV infection. The prognosis of advanced cases, especially those with distant metastasis, is still poor despite advancements in molecular research and its application to clinical settings. Thus, further advancement in basic and clinical research that may lead to novel therapeutic modalities is needed. Farnesylation is a lipid modification in the C-terminus of proteins. It enables proteins to attach to the lipid bilayer structure of cellular membranes. Farnesylation was initially identified as a key process of membrane association and activation of the RAS oncoprotein. Farnesylation is thus expected to be an ideal therapeutic target in anti-RAS therapy. Additionally, more and more molecular evidence has been reported, showing that proteins other than RAS are also farnesylated and have significant roles in cancer progression. However, although several clinical trials have been conducted in cancers with high rates of ras gene mutation, such as pancreatic carcinomas, the results were less favorable than anticipated. In contrast, favorable outcomes were reported in the results of a phase II trial on head and neck carcinoma. In this review, we provide an overview of the molecular pathogenesis of NPC in terms of the process of farnesylation and discuss the potential of anti-farnesylation therapy in the treatment of NPC.