Targeting the glycolytic enzyme PFKFB4 in liver cancer underlying p53 mutation: mechanistic insight and therapeutic implication

Dr Ho, Daniel Wai Hung   (Principal Investigator (PI))

Dr Chan Lo Kong   (Co-Investigator)

Professor Ng Irene Oi Lin   (Co-Investigator)

36

2020-06-01

1497150

Targeting the glycolytic enzyme PFKFB4 in liver cancer underlying p53 mutation: mechanistic insight and therapeutic implication

Glycolysis, Hypoxia, Liver Cancer, p53 mutation, PFKFB4

Others - Medicine, Dentistry and Health

07182546

Health and Medical Research Fund - Full Grant

2019

On-going

Hepatocellular Carcinoma (HCC) is one of the top lethal cancers in Hong Kong. HCC development is driven by the loss-of-function mutations in tumor suppressor genes including p53. The lack of a druggable driver mutation greatly limits the effectiveness of molecularly targeted therapy in advanced HCC. PFKFB4, a hypoxic inducible bi-directional glycolytic enzyme, was significantly upregulated in HCC tumors with p53 mutations and associated with aggressive tumor behaviors. We aim to investigate the mechanism underlying the PFKFB4 upregulation. Besides, the functional role of PFKFB4 and how it regulates the metabolic flux in the glycolytic pathway in the context of HCC will be investigated. More importantly, the therapeutic potential of using a first-in-class PFKFB4 inhibitor to treat p53 mutant HCC using relevant preclinical models will be examined.