Glasgow Scientists Uncover New Cancer Treatment Target in Grand Challenges Initiative

Researchers in Glasgow identify new target for treatment SCOTS scientists seeking answers to the mystery of why cancer occurs in certain parts of the body and not others may have found a new way to tackle some hard-to-treat cancers. The research team – part of the Cancer Grand Challenges initiative founded by Cancer Research UK and the National Cancer Institute, to take on some of cancer’s toughest challenges – focused on genetic faults that allow cancer to hijack a signalling system in the body which tells cells when, and when not, to grow. Cancer can then use that system, called the WNT pathway, to grow tumours in the intestine and liver. A new paper published in Nature Genetics has revealed that a protein called nucleophosmin (NPM1), which is involved in the control of growth, was found to be in high levels in bowel cancer and some liver cancers, due to the genetic errors in the WNT pathway. By blocking this protein, the team found that it may be possible to develop new treatments for specific cancers which hijack the body’s growth system through this genetic error. Lead researcher on the project Professor Owen Sansom, Director of the Cancer Research UK Scotland Institute and the University of Glasgow, and co-investigator for team SPECIFICANCER, said: “Because NPM1 isn’t essential for normal adult tissue health, blocking it could be a safe way to treat certain cancers, like some hard-to-treat bowel and liver cancers. “We found that if NPM1 is removed, cancer cells struggle to make proteins properly and this allows a tumour suppressor to activate, preventing cancer growth. “Increasing numbers of people are affected by these cancers, with some treatments unfortunately limited for some patients, so finding a new way to tackle these cancers is crucial.” Researchers at the Cancer Research UK Scotland Institute in Glasgow studied genes which can cause cancer, looking specifically at the bowel and liver, to discover why those genes only cause cancers in specific tissues. Part of the SPECIFICANCER project, which focuses on why some cancer-causing genes only cause cancers in specific tissues, this new research identified a way to target some of the genetic errors that cause hard-to-treat cancers in those organs. Scotland has one of the highest rates of bowel cancer, also known as colorectal cancer, and liver cancer in the UK. There are around 4,200 people in the UK diagnosed with bowel cancer each year. It remains the second most common cause of cancer death in Scotland, claiming around 1,700 lives annually. A recent study by the American Cancer Society published in The Lancet Oncology showed early-onset bowel cancer rates in adults aged 25-49 are rising in 27 of 50 countries studied and are rising faster in young women in Scotland and England than in young men. Around 670 people die from liver cancer each year in Scotland so finding more effective ways to tackle the disease is vital. Dr David Scott, Director of Cancer Grand Challenges, said: “Scientific breakthroughs like this demonstrate the power of Cancer Grand Challenges to bring together the world’s best minds to transform our understanding of how cancer starts and, crucially, how we treat it. “By scrutinising the fundamental processes that drive cancer, we can tackle the disease at its beginnings, driving progress towards real-world impact for people affected by cancer.” Proteins are essential for the body to build structures such as skin, hair or other tissue, but sometimes the body’s messaging system goes wrong, causing tumours to grow. This can be caused by mutations in the body’s messaging system, which then pass on the wrong instructions from our DNA, causing the cells to grow uncontrollably. SPECIFICANCER was co-funded by Cancer Research UK and the Mark Foundation for Cancer Research in 2019 to understand a central mystery in cancer biology – why some cancer-causing genes only cause cancers in specific tissues. For example, it is known that the BRCA genes can increase the risk of breast or ovarian cancer but not heart or skin cancers. The mechanisms have proved to be a mystery, and SPECIFICANCER is seeking patterns and vulnerabilities to find new treatments more personalised to a patient or particular area of the body. Bowel and liver cancers were the focus of this latest research, but the team hope its findings could be applicable to other cancers. The next step is to find medical treatments which block the production of the NPM1 protein. There are already existing treatments which can slow tumour growth so if a new drug can be discovered to target NPM1 in the same way, it could provide a safe and effective way to treat certain cancers.