Abstract
Nasopharyngeal carcinoma (NPC) is a rare malignancy with a distinct epidemiological pattern and is most often associated with Epstein-Barr virus (EBV). EBV plays a critical role in NPC pathogenesis, with viral proteins driving oncogenesis by altering immune regulation, apoptosis, and tumor progression. The unique molecular landscape of NPC presents both challenges and opportunities for therapeutic development, particularly in the recurrent and metastatic (R/M) setting, where treatment resistance remains a major hurdle. While platinum-based chemotherapy has traditionally been the standard of care for R/M NPC, immune checkpoint inhibitors (ICIs) have emerged as a key component of treatment. However, both intrinsic and acquired resistance to PD-1/PD-L1 blockade underscore the need for alternative strategies, including modulation of alternative immune checkpoints and simultaneous engagement of non-redundant pathways to enhance responses and durability. Leveraging EBV-driven biology, emerging immunotherapeutic approaches, such as EBV-specific adoptive cellular therapies and therapeutic vaccines, aim to induce durable immunity to viral proteins. Additionally, targeted therapies including receptor tyrosine kinase inhibitors, epigenetic modulators, and antibody-drug conjugates are redefining precision medicine by selectively delivering cytotoxic agents to tumors. With growing insights into the biology of NPC and evolving therapeutics, the integration of immunotherapy, targeted agents, and biomarker-driven strategies is poised to transform NPC treatment, emphasizing biology-driven, multimodal approaches to optimize patient outcomes.