Addressing Nasopharyngeal Carcinoma (NPC), the head and neck cancer that is so prevalent in Hong Kong and the South China region, a Cooperative NPC Research Centre was established with a joint grant from the Research Grant Council Central Allocation to the Hong Kong University of Science and Technology, Chinese University of Hong Kong, and the Hong Kong Baptist University.

The aims of the Centre were to better understand and more effectively treat NPC by –

• Gaining more knowledge on the molecular genetic basis of NPC by identifying chromosomal regions, genetic changes, and biomarkers associated with the clinical status of NPC patients, using molecular cytogenetic and molecular genetic approaches.
• Identifying tumor suppressive regions important for the development of NPC.
• Developing and evaluating the usefulness of assays to detect EBV (Epstein-Barr Virus) plasma DNA and EBV-associated mRNA (messenger Ribonucleic Acid) transcripts in NPC patients.
• Synthesizing and studying the role of photodynamic therapy sensitizers targeting the destruction of NPC cells.

Efforts so far have resulted in the identification of candidate tumor suppressor genes mapped to chromosome 11, such as THY1 and TSLC1. Their role in the development of NPC has been studied in cell growth, cell transformation, and the generation of tumors in cell samples; they are proving useful as predictors in the development of NPC.

Investigating the role of EBV, the Centre studied its effect on normal cells and the signaling pathways for cancer development. They discovered increased activity in cellular signaling molecules in EBV-infected cells with a number of downstream targets of these pathways being over-expressed. Additionally, inflammatory cytokines – the chemical messengers between cells that can stimulate or inhibit the growth and activity of various immune cells – were found to be suppressed in nasopharyngeal cells after EBV infection. The role of the EBV-encoded BARF1 gene was also examined

and found toffect anchorage independent growth abilities, cell migration and induces apoptosis, a form of programmed cell destruction.

The efficacy of using plasma EBV DNA detection for the diagnosis of EBV infection was studied in NPC patients undergoing concurrent radiotherapy and chemotherapy (RT/CRT) treatment. Patients with undetectable EBV DNA are expected to continue having undetectable EBV DNA at the end of the course of their RT/CRT, resulting in a positive prognosis. However, a proportion of patients with detectable EBV DNA at week 4 of their treatment are likely to have residual EBV DNA at the end of RT/CRT and the likelihood of ongoing NPC.

The Centre has also identified a potentially novel treatment for recurrent local NPC. A new photodynamic therapy (PDT) drug, Zn-BC-AM, has been synthesized. Its usefulness as a potential therapeutic agent, killing cancerous cells by apoptosis and cytokine recruitment, has been demonstrated on animals.

Discussing these developments, principal investigator, Centre Director and Chair Professor of Biology at HKUST, Maria Li Lung commented, "We are currently shortlisted for a NPC Area of Excellence proposal. This will include 23 members from HKUST, HKU, CUHK, and HKBU. Our aim is to coordinate basic cancer studies, NPC genomics and epigenetics, EBV diagnostics and therapeutic developments to better understand the molecular basis for NPC, develop biomarkers for its diagnosis and identify useful targets for molecular therapies. Understanding how the disruption of chromosomal stability, DNA replication and cell cycles contribute to cancer development and finding the genes contributing to NPC development will help to improve current treatment options, alleviate and reverse the side effects of radiotherapy treatment, and offer novel therapeutic options. We hope that this HK-wide consortium dedicated to NPC research, will allow us to translate our basic findings into clinically useful applications that will improve the treatment and survival of NPC patients."

Prof. Maria Li Lung
Department of Biology,
The Hong Kong University of Science and Technology
bomaria@ust.hk