Liver cancer is one of the most common cancers worldwide and incidence is increasing dramatically in the Gulf region.
As treatment options are limited Al Jalila Foundation awarded a research grant to Dr Kirsten Sadler Edepli from New York University Abu Dhabi who is looking at targeting the epigenetic changes and genomic instability that occurs in hepatocellular carcinoma as a promising avenue for developing new therapies.
The research aims to provide an understanding of how epigenetic changes lead to cancer. The team focus on the epigenetic regulator and oncogene, UHRF1, which is overexpressed in all human solid tumors, including hepatocellular carcinoma.
Using zebrafish to decipher how UHRF1 causes cancer by overexpressing UHRF1 in hepatocytes, this model enables investigation into how precancerous cells develop, and how they are converted to malignant, tumor forming cells.
The study found that UHRF1 overexpression activates senescence as a tumor suppressive mechanism and stops hepatocyte proliferation, accompanied by the activation of DNA damage repair mechanisms. DNA damage response is required for senescence induction and a pro-inflammatory immune signature and the recruitment of immune cells to the pre-cancerous liver tissue may halt tumor growth by eliminating cells damaged by high levels of UHRF1. Unfortunately, senescence can be bypassed so that precancerous cells can develop into cancer. Cells which are damaged by UHRF1 overexpression become malignant and form tumors. The investigation in the mechanism of senescence bypass continues, which is an important area to target to prevent pre-cancerous lesions from developing into tumors.
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