A research team, led by Professor Dai Wei (front right), has discovered that the Epstein-Barr virus (EBV), a common human virus closely linked to nasopharyngeal carcinoma (NPC), can change the 3D structure of the human genome inside cancer cells. This groundbreaking finding reveals the mechanism by which EBV actively promotes cancer progression and offers promising avenues for developing targeted therapies for patients, with the aim of saving even more lives.
Researchers from the Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, LKS Faculty of Medicine of the University of Hong Kong (HKUMed), have discovered that the Epstein-Barr virus (EBV), a common human virus closely linked to nasopharyngeal carcinoma (NPC), can change the 3D structure of the human genome inside cancer cells, much like assembling building blocks. This groundbreaking finding reveals the mechanism by which EBV actively promotes cancer progression and offers promising avenues for developing targeted therapies for patients, with the aim of saving more lives. The findings were published in the scientific journal Nature Communications [link to publication].
The hidden threat of EBV in nasopharyngeal carcinoma
Over 95% of adults are infected with EBV at some point in their lives, often during childhood or adolescence. While most infections are mild or asymptomatic, EBV is linked to several types of cancer, notably NPC. This cancer develops in the nasopharynx, which is behind the nose, and is especially prevalent in southern China. While radiotherapy and chemotherapy are common treatments, metastasis – the spread of cancer – remains a major challenge. Seven to 20% of patients experience metastasis, which reduces the five-year survival rate from 80–90% down to just 20–30%. EBV is consistently found in NPC cells, but it does not integrate into the human DNA. Instead, it floats inside the cell's nucleus, like an 'island' (called extrachromosomal DNA), and produces only a few proteins (such as EBNA1), allowing it to stay hidden from the immune system while subtly affecting the cell.
Decoding EBV's role: the 'hooking' mechanism that promotes cancer spread
To understand how EBV drives cancer spread, the research team deployed cutting-edge genomic technologies to study how the virus interacts with human DNA inside cancer cells. They found that EBV physically hooks onto DNA and reorganises its 3D structure in a very precise way. This restructuring affects the 'switches' that control how cells behave. Hooking onto the DNA in this way enables EBV to hijack the cell's epigenetic system, helping the virus survive and promoting tumour growth.
By analysing tumour samples from 177 patients recently diagnosed with NPC in hospitals across Hong Kong and Guangzhou, the researchers identified a new risk factor and a set of key human genes regulated by EBV – referred to as 'genomic signature markers' – which can help predict the likelihood of cancer metastasis. These genes give tumour cells dual characteristics: they allow the cells evade the immune system and facilitate their spread more easily.
Future therapies: targeting EBV's 'hooking' mechanism
Metastasis is the leading cause of death in patients with NPC. Despite treatment options such as radiotherapy, chemotherapy and emerging immunotherapies, patients with metastatic NPC usually have poor survival rate. Additionally, current treatments have significant side effects and resistance issues.
Professor Dai Wei, Assistant Professor in the Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, HKUMed, said, 'EBV is not just a passive passenger. It is a key driver of NPC progression, as it actively drives cancer by physically hooking onto the genome and hijacking cellular systems.'
'We used epigenetic drugs and a precise gene editing tool, called CRISPR, to break down the connection between EBV and cancer cells,' added Professor Dai. 'Disrupting EBV's genome "hooking" effectively reduced the amount of virus and slowed down tumour growth. This proves that targeting EBV's "hooking" mechanism could be a promising way to treat this cancer. Additionally, predictive models based on EBV-regulated genes can help clinicians identify high-risk patients and tailor personalised therapies.'
The research team plans to explore further how EBV hooks onto the genome and what happens afterwards, with the goal of developing new therapies that prevent NPC metastasis at its root.
About the research team
This research was supervised by Professor Dai Wei, Assistant Professor, and Dr Dittman Chung Lai-shun, Dr Hou Zhaozheng, Kazi Anisha Islam, Dr Liu Songran, joint-first authors, all from the Department of Clinical Oncology, Centre of Cancer Medicine, School of Clinical Medicine, HKUMed. The study was carried out in collaboration with Professor Ng Wai-tong, Professor Dora Kwong Lai-wan, Professor Annie Lee Wing-mui, Professor Victor Lee Ho-fun, and Professor Guan Xinyuan from the same department; Professor Liu Zhonghua from the Department of Biostatistics, Columbia University (New York, USA); Professor Chen Honglin from the Department of Microbiology, School of Clinical Medicine, HKUMed; and Professor Xia Yunfei from the Sun Yat-sen University Cancer Centre (Guangzhou, PRC).
Acknowledgements
The research was supported by multiple funding bodies, including Hong Kong's Research Grants Council, the Health Bureau, the HKU Startup Fund, the Guangdong and Shenzhen Science Programmes, and the InnoHK initiative.
