Starving livers of glucose for HCC prevention and treatment

Start date: 16 November 2020
End date: 30 November 2024
Value: £50,000
Partners and collaborators: Funder: Guts UK
Primary investigator: Dr Salvatore Papa
External co-investigators: Dr Concetta Bubici (Brunel University of London); Prof Derek Mann (Newcastle University)
Postgraduate students: Fatma Kaci

Description

Chronic liver injury triggers a repair response that leads to liver fibrosis (i.e., liver scarring). This repair response occurs as a result of various insults including toxins, autoimmune disorders, viral infections, and leads to the development of fibrosis, cirrhosis (late stage fibrosis), and, ultimately, liver cancer. Liver cancer includes hepatocellular carcinoma (HCC) and intrahepatic bile duct cancer (also known as intrahepatic cholangiocarcinoma, ICC). Understanding how fibrosis and cirrhosis develops from healthy normal liver and progresses to liver cancer is particularly relevant for identifying chemo-preventive therapies. Cellular metabolism plays an important role in cell survival, proliferation, and growth. We and others have shown that the progression of fibrosis/cirrhosis to liver cancer is accompanied with a progressive change (reprogramming) in the metabolism of the liver. Both fibrotic liver and liver cancer rely on an accelerated uptake and consumption of glucose to produce energy and sustain cell survival (as opposed to cell death). Therefore, our hypothesis is that targeting oncogenic signalling pathways that negatively impact on the altered cellular metabolism of diseased liver may be useful for the treatment of liver fibrosis and cancer. Our overall objective of this study is therefore to establish a mechanistic link between metabolic reprogramming, apoptosis-resistance and compensatory proliferation during the progression from fibrosis/cirrhosis to liver cancer.

https://theconversation.com/bile-duct-cancer-existing-leukaemia-treatment-could-hold-promise-mouse-study-162201

Impact

In a major new study published in Hepatology our research group proposes that the drug all-trans retinoic acid (ATRA) could be used to help treat bile duct cancer.

Downloads

83721-PB4-4346-R3_anonymous.pdf
arif-et-al-2021-targeting-myosin-1c-inhibits-_anonymous.pdf
fcell-09-684049_anonymous.pdf
Liver International - 2024 - Coombes - Osteop_anonymous.pdf
phosphorylation_and_stabilization_of_pin1_by__anonymous.pdf

Project website

https://gutscharity.org.uk/research/current-active-research/liver-cancer-dr-salvatore-papa/