Reactivation of Epstein-Barr virus (EBV) lytic cycle in EBV-associated epithelial malignancies by iron chelators and evaluation of its therapeutic potential

Dr Chiang, Alan Kwok Shing   (Principal Investigator (PI))

Dr Hui Kwai Fung   (Co-Investigator)

Professor Yang Dan   (Co-Investigator)

30

2017-05-01

2021-02-25

1196944

Reactivation of Epstein-Barr virus (EBV) lytic cycle in EBV-associated epithelial malignancies by iron chelators and evaluation of its therapeutic potential

EBV, Gastric carcinoma, Iron chelator, Lytic reactivation, NPC

Others - Medicine, Dentistry and Health

16150472

Health and Medical Research Fund - Full Grant

2016

Completed

Objectives: We aim to investigate the downstream events after iron chelation which lead to EBV lytic cycle reactivation by iron-chelating chemicals in NPC and GC cells and evaluate the therapeutic value of iron chelators to EBV-positive epithelial malignancies. Methods: Candidate genes (e.g. HIF-1a and NDRG1) mediating lytic reactivation by iron chelators will be verified by specific knockdown or overexpression to examine their essentiality and sufficiency in mediating EBV lytic reactivation. Effects of iron chelators alone and in combination with the anti-viral drug ganciclovir to the growth EBV-positive and –negative tumour cells will be examined both in vitro and in vivo. Cell death pathways leading to killing of tumour cells will be examined with various molecular techniques. Outcomes: The findings will provide fundamental knowledge on the mechanism of EBV lytic reactivation by a new class of lytic inducers, the iron chelators, in EBV-positive epithelial malignancies and the necessary impetus to devise new virus-targeted strategies against the virusassociated cancers.