Mark Jacqueline Kar Kei, Teh Aik-Hong, Yap Beow Keat
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia.
Centre for Chemical Biology, Universiti Sains Malaysia, 11900, Bayan Lepas, Penang, Malaysia.
Med Oncol. 2025 Jan 31;42(3):59. doi: 10.1007/s12032-025-02610-x.
Nasopharyngeal carcinoma (NPC) is a distinctive epithelial cancer closely associated with Epstein-Barr Virus (EBV) infection, posing significant challenges in diagnosis and treatment due to its resistance to conventional therapies and high recurrence rates. Current therapies, including radiotherapy and chemotherapy, exhibit limited efficacy, particularly in recurrent or metastatic cases, highlighting the urgent need for novel therapeutic strategies. Targeting EBV oncoproteins, such as Epstein-Barr Virus encoded Nuclear Antigen 1 (EBNA1), Latent Membrane Protein 1 (LMP1), and Latent Membrane Protein 2 (LMP2), presents a promising therapeutic avenue in NPC treatment. This review discusses the latest advancements in drug discovery targeting EBV oncoproteins, emphasizing the identification of inhibitors for specific functional regions of oncoproteins EBNA1, LMP1, and LMP2. Particular attention is given to the molecular mechanisms of these inhibitors and their preclinical or clinical potential in treating EBV-positive NPC. These developments highlight a promising future for targeted therapies in improving outcomes for NPC patients.
鼻咽癌(NPC)是一种与爱泼斯坦-巴尔病毒(EBV)感染密切相关的独特上皮性癌症,由于其对传统疗法具有抗性且复发率高,在诊断和治疗方面面临重大挑战。目前的疗法,包括放疗和化疗,疗效有限,尤其是在复发或转移的病例中,这凸显了对新型治疗策略的迫切需求。靶向EBV癌蛋白,如爱泼斯坦-巴尔病毒编码的核抗原1(EBNA1)、潜伏膜蛋白1(LMP1)和潜伏膜蛋白2(LMP2),在鼻咽癌治疗中展现出一条有前景的治疗途径。本综述讨论了靶向EBV癌蛋白的药物研发的最新进展,重点强调了针对癌蛋白EBNA1、LMP1和LMP2特定功能区域的抑制剂的鉴定。特别关注这些抑制剂的分子机制及其在治疗EBV阳性鼻咽癌中的临床前或临床潜力。这些进展凸显了靶向治疗在改善鼻咽癌患者治疗效果方面的光明前景。