A groundbreaking study from The University of Hong Kong's LKS Faculty of Medicine has revealed a sophisticated mechanism by which the Epstein-Barr virus (EBV) actively drives the progression and metastasis of nasopharyngeal carcinoma (NPC). Published in 2024, the research indicates that EBV, a virus infecting over 95% of the global adult population, acts as a "dynamic architect" by physically reconfiguring the three-dimensional structure of the human genome within cancer cells.
The study found that EBV, which exists as extrachromosomal DNA (ecDNA) in NPC cells, physically "hooks" onto specific regions of human chromatin. This interaction remodels the genome's architecture, influencing epigenetic switches that control gene expression. This hijacking of the host cell's epigenetic machinery is reported to promote viral persistence, fuel oncogenic processes, aid in immune evasion, and significantly enhance the potential for metastasis.
Findings were validated by analyzing tumor samples from 177 NPC patients from Hong Kong and Guangzhou, identifying genomic signature markers that can predict the risk of metastasis. Nasopharyngeal carcinoma, prevalent in Southern China, presents significant clinical challenges due to its propensity for metastasis. While initial treatments like radiotherapy and chemotherapy can be effective, metastatic NPC patients face a reduced five-year survival rate, often between 20-30%.
Led by Professor Dai Wei, the research shifts the understanding of EBV from a passive bystander to an active agent in cancer development, clarifying mechanisms by which EBV influences genome architecture, which had previously remained an enigma. In a significant therapeutic development, researchers utilized epigenetic drugs and the CRISPR-Cas9 gene-editing system to disrupt the viral-host genomic connection.
These interventions successfully reduced EBV presence in cancer cells and slowed tumor growth, demonstrating the potential for targeted therapies that interfere with this viral-host interaction. This approach could offer a more precise and potentially less toxic alternative to conventional treatments, which often struggle with resistance and side effects. The implications of this research extend to personalized medicine, with the identified genomic markers offering a pathway to better predict metastasis risk and tailor treatments accordingly.
The broader scientific community anticipates that these findings will advance viral oncology and cancer epigenetics, paving the way for improved clinical outcomes in virus-associated cancers. Further research is planned to elucidate the exact molecular details of the hooking mechanism and downstream signaling cascades, aiming to uncover additional therapeutic targets to combat metastasis.