Tag: Cancer Research UK Scotland Institute

Genetic mutation focus on new cancer study

Researchers search for way to stop bowel cancer growing

SCIENTISTS in Glasgow are launching a new Cancer Research UK-funded project to find a way to stop bowel cancer cells hijacking the body.

The team, based at the Cancer Research UK Scotland Institute in the city, will focus on a particular system inside the human body, called the Wnt pathway – a key messaging system controlling growth.

A specific genetic mutation can cause this system to tell cells to grow and produce new cancer cells out of control.

The cancer cells then hijack the pathway and prevent it from growing healthy cells, effectively starving the body of healthy growth.  This can eventually lead to the growth of tumours in the lining of the bowel.

Dr Nadia Nasreddin, researcher at the Cancer Research UK Scotland Institute in Professor Sansom’s group, said: “We hope to find a way to help healthy cells fight the mutant cell colonisation of the bowel lining, by using drugs that can promote healthy cell growth.

“If we boost the Wnt pathway in normal cells, we can improve their health, restore their capacity to divide and produce new healthy cells, and reduce the ability of cancer cells to grow in the bowel.”

With funding of £357,759 from Cancer Research UK, the project will help tackle bowel cancer, also known as colorectal cancer, the second most common cause of cancer deaths in the UK.*

Treatment options for bowel cancer remain limited, particularly for patients who are diagnosed at later stages of the disease, making the search for new therapies vital. Scotland is disproportionately affected by the disease with around 4,000 people diagnosed each year. **

Bowel cancer is caused by changes in the DNA (called mutations) in important cells in the intestine called intestinal stem cells.

These cells maintain the intestine’s lining by constantly dividing to replace old or worn-out cells with healthy new ones. These cells live within a specific environment, characterised by high activity of the Wnt pathway.

Eighty per cent of colon cancer cases are caused by mutations in a particular gene which is responsible for controlling the Wnt pathway environment and can be inherited.

When this mutation occurs, it creates a very high Wnt environment which results in the cell’s dividing and producing new cells faster than normal.

It also produces a molecule that deprives normal cells of their Wnt environment causing normal intestinal stem cells to stop dividing and producing new ones.

This results in mutant cells in the lining of the intestine that, over time, replace the normal cells eventually forming into a tumour.

The team will test four different molecules to determine which best supports the health of normal intestinal stem cells in mouse models.

Researchers will further develop any which show a clear benefit to survival into drugs for human use.

Science engagement lead at Cancer Research UK, Sam Godfrey, said: “We are delighted to fund this exciting research project which looks at the beginnings of cancer and seeks ways to prevent it developing.

“Harnessing our own body’s power to support healthy growth and halt the excessive growth which results in tumours could lead to the kind of breakthrough which transforms the way we see, and treat, bowel cancer.”

Bowel cancer kills 16,800 people in the UK (1,700 in Scotland) every year and is increasingly being diagnosed in younger people.*

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.**

Groundbreaking research could revolutionise bowel cancer treatment

New research led by a team of scientists from Queen’s University Belfast and the Cancer Research UK (CRUK) Scotland Institute in Glasgow have made a series of groundbreaking discoveries into tumour biology that may be used to deliver a more effective personalised medicine approach for patients with bowel (colorectal) cancer.

Bowel cancer is the fourth most common cancer in the UK, with around 42,900 new bowel cancer cases and around 16,600 bowel cancer deaths in the UK every year, a statistic that highlights the need for new ways to treat patients with this aggressive disease.

The new study, funded by Cancer Research UK and published today in the prestigious journal Nature Genetics, used a unique and innovative approach developed in Belfast, to identify a set of previously unseen molecular patterns in tumour tissue that provides new information related to treatment response and risk of disease progression.

These remarkable results mean that clinicians and scientists can now draw more information from a patient’s tumour tissue which may lead to better treatment options.

Previously, the most common approach for identifying groups of tumours based on their biological signalling, known as molecular subtyping, used information about how active individual genes are within tumour tissue.

The subtypes identified using this method have shaped understanding of cancer development, progression and response to therapy over the last decade and served as the basis for numerous clinical trials and pre-clinical studies.

Dr Philip Dunne, Reader in Molecular Pathology from the Patrick G Johnston Centre for Cancer Research at Queen’s University Belfast and senior author of the study, explains: “While looking at patterns across individual genes has revealed remarkable insights into cancer signalling, advances in laboratory research over the last decade have shown that assessing activity in groups of closely related genes in combination can provide new understanding that isn’t apparent when using the traditional single gene approaches.”

Given the potential value of this new pathway approach, researchers from Queen’s University Belfast, the CRUK Scotland Institute, University of Zurich, University of Oxford alongside a multinational collaborative group proposed a new data-driven method for reclassification of bowel cancer, which has been published in this new groundbreaking study.

By assembling genes into biological pathways prior to the development of molecular subtypes, the team rearranged tumours into a series of new groups, based on activity across a complex network of cancer-related signalling; all of which appears to be critical in predicting how well a tumour will respond to different treatments such as chemotherapy and radiotherapy.

To ensure that scientists and clinicians around the world can immediately access these data and test this new subtyping approach, the team have released a freely available classification tool that allows the Belfast-developed approach to be used on tumour samples in any research lab.

Dr Sudhir Malla, Postdoctoral Research Fellow from the Patrick G Johnston Centre for Cancer Research at Queen’s University Belfast and first author of the study commented: “By developing an unrestricted classification tool for the cancer research community, it means that researchers from around the world can reproduce our finding on data emerging from their own collections of tumour samples, to identify biological pathways that cancer cells switch on or off to control their movement, growth and response to their environment.”

Professor Owen Sansom, Director of the Cancer Research UK Scotland Institute in Glasgow, who co-authored the study said: “The research presented today in Nature Genetics exemplifies the value of collaborative research between scientists and clinicians.

“Studies such as this are essential to enable us to understand the complexities of a patient’s tumour and will be used in our pre-clinical laboratories to identify novel treatments specifically targeting the biological patterns we have identified.”

Dr Sam Godfrey, Research Information Lead at Cancer Research UK, said: “Cancer is perhaps the most complex disease we face, and no single treatment will ever beat it.

“Cancer Research UK is delighted to have funded this innovative research, an important step towards giving doctors the insight to see which therapy can best exploit an individual cancer’s weakness.

“Research like this could lead to better and more precise treatments for the thousands of people diagnosed with bowel cancer every year in Scotland.”

The team are now applying their new subtyping approach on tumour samples derived from clinical trials run in the UK, to build the essential clinical evidence needed before the new method can be used to make clinical decision about which treatments a patient should be offered.