QUB breakthrough in cancer research

Research led by Queen’s University Belfast has found a new way through which the p53 gene, the most frequently mutated gene in cancer, can prevent cell death in colorectal cancer. Following this new discovery, the research team have identified new treatments that may improve the effectiveness of chemotherapy given to patients to treat colorectal cancer.

By The Newsroom
Thursday, 23rd July 2020, 8:00 am

The research was jointly led by principal investigators, Dr Simon McDade and Professor Daniel Longley’s Research Groups from the Patrick G Johnson Centre for Cancer Research.

The tumour suppressor gene p53 normally tells cells to stop growing or die in response to cancer-causing stresses, such as DNA damaging UV light from the sun. However, how and why the 50 per cent of colorectal cancers in which p53 is not mutated suppress its ability to induce cell death remains poorly understood, until now. The research team found that when colorectal cancer cells in which p53 is not mutated are treated with chemotherapy, they become highly reliant on increased levels of a protein called FLIP for survival. In colorectal cancer cells, FLIP levels are increased by p53 itself, paradoxically blocking p53-induced cancer cell-death. This reliance on FLIP can be exploited with drugs called HDAC inhibitors that block p53-induced expression of FLIP but maintain activation of cell-death. This enhances the ability of chemotherapy to kill cancer cells. The research provides evidence for future clinical trials combining p53 activating therapies, such as chemotherapy.