Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC. In light of these developments, it has become evident that a deeper understanding of the tumor microenvironment (TME) is crucial. The TME serves a dual function, acting as a promoter of tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression and enabling immune evasion. Consequently, a comprehensive comprehension of the TME and its intricate involvement in the initiation, progression, and metastasis of NPC is imperative for the development of effective anticancer drugs. Moreover, given the complexity of TME and the inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy and circumvent drug resistance. This review aims to provide an in-depth exploration of the TME within the context of EBV-induced NPC, with a particular emphasis on its pivotal role in regulating intercellular communication and shaping treatment responses. Additionally, the review offers a concise summary of drug resistance mechanisms and potential strategies for their reversal, specifically in relation to chemoradiation therapy, targeted therapy, and immunotherapy. Furthermore, recent advances in clinical trials pertaining to NPC are also discussed.