Our Impact

Why is this research important?

Idiopathic Inflammatory Myopathy (IIM) is a rare autoimmune condition that causes inflammation and affects muscles, skin and the lungs. It is associated with a high risk of cancer and causes significant disability for patients.

Although IIM is treatable, there is no cure and cancer is the leading cause of death. It affects approximately 10,000 people in the UK and current evidence shows that up to 25% of patients will develop cancer within 3 years of disease onset. Lymphoma, lung, ovarian, bowel and breast cancers are the most commonly associated cancers. The risk of cancer outside 3 years of disease onset is similar to that of the general population.

What did we do?

Building on research from the Rheumatic and Musculoskeletal Disease (RMD) Theme of the NIHR Manchester BRC, the first international cancer screening guideline was developed for clinical practice as studies had shown 83% of IIM-associated cancers were in their later stages when diagnosed. Detecting cancer early is a priority for improving patient outcomes and survival.

Led by Dr Alexander Oldroyd, from Manchester BRC’s RMD Theme, the ‘Idiopathic Inflammatory Myopathy-Associated Cancer Screening: an International Myositis Assessment and Clinical Studies Group Initiative’ guideline was published in November 2023.

The guideline groups patients into standard, moderate, or high-risk categories based on their disease type and certain clinical features. Patients can then be screened with a basic test such as a chest X-ray or a more advanced technique such as a CT scan. The timing and frequency of the screening tests are guided by the risk category which helps clinicians to plan appropriately.

The guideline was developed by an international expert group, which included several Manchester BRC researchers which highlights our capability in bringing together experts in musculoskeletal disease, cancer and rare conditions from across different Themes and Clusters.

This guideline could help save lives by enabling earlier cancer diagnosis and could also avoid expensive tests where these are not needed, resulting in healthcare savings to the NHS.

Read this news story to find out more about the guideline.

What will we do next?

The next steps are to test how well the guideline works to identify cancers in patients with IIM from around the world.

Dr Oldroyd is leading the MyoScreen Study (funded by Cancer Research UK), which aims to investigate the role of liquid biopsy – or blood tests – as a method of early cancer detection, to see if these can improve the detection of cancer even further.

There are also plans to support the team in securing further funding to ensure the guideline recommendations are implemented across the UK.

Why is this research important?

Approximately 100,000 people in the UK each year will have a stroke – a serious life-threatening condition that happens when the blood supply to part of the brain is cut off by a blood clot. Strokes affect more than 6,000 people in Greater Manchester each year and those affected are at increased risk of further severe strokes and heart attacks in the following hours, days and weeks.

An innovative bedside genetic test could dramatically improve outcomes for thousands of people in the UK affected by stroke each year. Developed by Manchester researchers in collaboration with Manchester-based company genedrive plc, the test can tell healthcare professionals in approximately 1 hour if stroke patients will benefit from clopidogrel, the current first-line treatment to prevent recurrence.

Clopidogrel prevents platelets (a type of blood cell) from sticking together and forming a dangerous blood clot. However, around 29% of all patients in the UK (and up to 60% in different ethnic groups) have a change in the CYP2C19 gene which reduces clopidogrel’s effectiveness.

Individuals carrying changes in the CYP2C19 gene are also twice as likely to have further strokes when treated with clopidogrel. If these genetic changes can be detected before treatment, then doctors can use an alternative, more effective medicine.

What did we do?

Building on the work by the NIHR Manchester Biomedical Research Centre’s (BRC) Next Generation Phenotyping and Diagnostics Theme (NGPD), which focuses on making pharmacogenetic testing more accessible to patients to improve clinical outcomes, the rapid point of care genetic test for this gene was developed in collaboration with genedrive.

Using a simple cheek swab, this non-invasive test can be performed at the bedside. From the swab, the Genedrive system interprets the genetic information from the patient and informs the clinician with options on the course of treatment within one hour. Previously, genetic testing for CYP2C19 could only be carried out using specialist laboratories, a process which can take several days. Patients with CYP2C19 variants need to be identified quickly so alternative treatments can be used.

Professor Bill Newman, Rare Conditions Co-Theme Lead at the NIHR Manchester BRC led the pilot project, which has now been recommended for use in the NHS by the National Institute for Health and Care Excellence (NICE), representing a major transformation in the way we manage stroke in this country.

Read this news story to find out more about the genetic test.

What will we do next?

Genomic medicine is changing the future of healthcare.

This research is part of the DEVOTE programme, an Innovate UK funded project coordinated by Health Innovation Manchester, led by The University of Manchester and supported by Manchester University NHS Foundation Trust (MFT), which hosts Manchester BRC.

The innovative test was used successfully over 6 months at Manchester Royal Infirmary and the Manchester Centre for Genomic Medicine at Saint Mary’s Hospital, both part of MFT.

Further evaluation will be carried out at Greater Manchester’s Hyper Acute Stroke Unit (HASU) at Salford Royal Hospital, part of Northern Care Alliance NHS Foundation Trust, which is also a partner Trust of Manchester BRC.

This is an important step in understanding the set-up costs, workforce and other requirements to roll out this innovation wider.

Prof Newman leads the ‘Clinical Validation of Translatable Diagnostic Methodologies Programme’ within Manchester BRC’s NGPD Theme, which will continue to support this research.

Why was industry collaboration so important?

Dr Gino Miele, Chief Scientific Officer, genedrive plc, said: “The collaboration of our company with the research and clinical team is a shining example of the NHS collaborating with a commercial company, from early product development through to clinical validation in real-world settings, to deliver real improvements in patient outcomes in a cost-effective way.”

Why is this research important?

Cancer of unknown primary (CUP) is where cancer has been found in the body (the secondary cancer), but current standard tests can’t identify where the cancer started (the primary cancer).

CUP is the 6^th leading cause of cancer death in the UK and patients from the country’s most deprived regions are more affected. Between 2-5% of new cancer diagnoses are CUP.

Treatment options for patients with CUP are limited because without knowing where the primary tumour is, we can’t use treatments that target a specific cancer type, which are more likely to work. This means around 80% of patients with CUP cannot be aligned to a known tumour type so receive standard chemotherapy treatment.

What did we do?

Researchers from Manchester BRC’s Cancer Precision Medicine Theme developed a new blood test that can accurately predict where the primary tumour is in patients with CUP.

The blood test, called CUPiD, can identify DNA which has been released from tumour cells into the bloodstream and analyse this to find out which type of cancer the DNA came from.

In a pilot study of 41 patients with CUP, the test predicted where the primary tumour was in 32 cases. For 23 of these cases, the prediction was consistent with the primary cancer type clinicians had suspected or that was later identified through other tests.

In 6 out of the 32 patients, the primary tumour was predicted where no diagnosis had been suspected. These were tumour types that have radically different treatment options to the standard chemotherapy recommended for CUP.

For around 9,000 cases of CUP diagnosed in the UK each year, this blood test has the potential to speed up diagnosis and enable better treatment options for patients.

This may result in improved management of the disease and patient outcomes, as well as reducing the uncertainty and psychological challenges patients experience when going through a diagnosis of CUP.

It also means that repeated biopsies (removing a piece of tumour for testing) wouldn’t be needed, which can be invasive, and therefore improves patient safety.

In collaboration with Vocal, the team have recently set up and run the first UK Patient and Public Involvement and Engagement CUP group, known as ‘CUP Club’. The group’s feedback on streamlining diagnosis through using a blood test has been positive and they encourage further research in this area.

The researchers have also worked closely with The CUP Foundation, an information resource providing support to CUP patients, their families and friends.

Read more about this research:

• Cancer Research UK in-depth article
• Meet Dr Alicia-Marie Conway, Manchester Cancer Research Centre blog

What will we do next?

The next steps are to improve the turnaround time and sensitivity of the blood test.

A Manchester BRC PhD student will test the performance of the blood test in a larger group of patients who have known tumours and those with CUP.

Further funding has been secured for this ongoing development and translation into clinical practice through the Cancer Research UK National Biomarker Centre at The University of Manchester and the NIHR Rosetrees Trust Advanced Fellowship, awarded to Manchester BRC researcher Dr Natalie Cook.