New and innovative ways to detect and treat cancer being trialled at the University of Birmingham are to receive renewed funding from Cancer Research UK and the NIHR.

The Birmingham Experimental Cancer Medicine Centre (ECMC), jointly funded by Cancer Research UK and the National Institute for Health and Care Research in England, provides world-leading expertise in the development of innovative cancer trials. New funding will enable the Birmingham ECMC to continue to conduct the highest quality trials into experimental treatments for cancer over the next five years.

The centre aims to be an integrated translational hub for cancer research in Birmingham and brings together the University of Birmingham’s global expertise in cancer research and strength in clinical trials to deliver accelerated patient benefit regionally, across the ECMC network and globally.

The centre is part of world-leading cancer research infrastructure in Birmingham alongside the Birmingham Cancer Research Clinical Trials Unit (CRCTU) and the NIHR Biomedical Research Centre. The funding enables the University of Birmingham, working closely together with organisations across the Birmingham Health Partners network, to focus on three themes in experimental cancer medicine: Precision Medicine, Cancer Immunotherapy and Biomarker-driven patient stratification.

Gary Middleton, Professor of Medical Oncology and Centre Director for the Birmingham Experimental Cancer Medicine Centre said:

“Thanks to the funding from Cancer Research UK and the National Institute for Health and Care Research we will be able to continue to design and deliver trials that have the power to make a huge difference to the lives of cancer patients.

“Over the past five years we have already made significant advances in precision medicine for cancer including through the National Lung Matrix trial. With renewed funding we will be able to drive forward the next generation of these studies, offering access to personalised therapies to cancer patients in the West Midlands and across the national ECMC network.”

Case study: Lung Matrix Trial

Executive Director of Research and Innovation at Cancer Research UK, Dr Iain Foulkes, said:

“We are proud to be supporting an expansion of our successful ECMC network, bringing together vast medical and scientific expertise to translate the latest scientific discoveries from the lab into the clinic.

“The ECMC network is delivering the cancer treatments of the future, bringing new hope to people affected by cancer. The trials taking place today will give the next generation the best possible chance of beating cancer.

Chief Executive of the NIHR, Professor Lucy Chappell, said:

“The ECMC Network is a vital strategic investment in the UK’s cancer research community, bringing together top scientists and clinicians to tackle some of the biggest scientific challenges in cancer and improve outcomes for patients.

“Through this route, we enable more people to join trials that could help them. The ECMC Network will give access to brand new experimental treatments for patients, including children and young people, paving the way for these treatments to be used in the clinic one day. This is a crucial part of NIHR’s work, and enables more people to join trials that might help them. We are proud to be partnering with Cancer Research UK and the Little Princess Trust in funding this network.”

Building on success

Birmingham is part of a network of 17 ECMCs across the UK, funded by Cancer Research UK and the NIHR, which deliver clinical trials of promising new treatments. Since 2007, when the network was first established, around 30,000 patients have taken part in 2,100 trials.

The funding will allow new, experimental treatments – including immunotherapies – for a wide variety of cancers to be developed, as well as improve existing treatments.

ECMCs work in conjunction with local NHS facilities to provide access to cutting-edge cancer treatments. Testing these treatments helps to establish new ways of detecting and monitoring the disease and to evaluate how it responds to the treatment.

DETERMINE

The University of Birmingham is part of a newly announced partnership which is running a multi-drug, precision medicine platform trial for adults and children with rare cancers who have run out of other treatment options.

The DETERMINE trial is one of the largest precision medicine platform trials targeting these populations and it will enrol patients who have an identifiable genetic alteration in their cancer that can be targeted by treatments that are already approved for use in other cancer types.

The trial is aiming to recruit patients with rare adult and paediatric cancers, as well as more common cancers with rare genetic alterations that could be targeted by the drugs being studied in the trial.

Scientists from BHP and Oxford University have made the first bone marrow ‘organoids’ that capture the key features of human bone marrow. The technology, for which University of Birmingham Enterprise has filed a patent application, will allow for the screening of multiple anti-cancer drugs at the same time, as well as testing personalised treatments for individual cancer patients.

A study, published in the journal Cancer Discovery, describes the new method; a process resulting in the production of an organoid that faithfully models the cellular, molecular and architectural features of myelopoietic (blood cell producing) bone marrow.

The research also showed that the organoids provide a micro-environment that can enable the survival of cells from patients with blood malignancies, including multiple myeloma cells, which are notoriously difficult to maintain outside the human body.

First author Dr Abdullah Khan, a Sir Henry Wellcome Fellow at BHP founder-member the University of Birmingham, said: “Remarkably, we found that the cells in their bone marrow organoids resemble real bone marrow cells not just in terms of their activity and function, but also in their architectural relationships – the cell types ‘self-organise’ and arrange themselves within the organoids just like they do in human bone marrow in the body.”

This lifelike architecture enabled the team to study how the cells in the bone marrow interact to support normal blood cell production, and how this is disturbed in bone marrow fibrosis (myelofibrosis), where scar tissue builds up in the bone marrow, causing bone marrow failure. Bone marrow fibrosis can develop in patients with certain types of blood cancers and remains incurable.

Senior study author Professor Bethan Psaila, a haematology medical doctor as well as a research Group Leader at the Radcliffe Department of Medicine, University of Oxford, said: “To properly understand how and why blood cancers develop, we need to use experimental systems that closely resemble how real human bone marrow works, which we haven’t really had before. It’s really exciting to now have this terrific system, as finally, we are able to study cancer directly using cells from our patients, rather than relying on animal models or other simpler systems that do not properly show us how the cancer is developing in the bone marrow in actual patients.”

Dr Khan also added: “This is a huge step forward, enabling insights into the growth patterns of cancer cells and potentially a more personalised approach to treatment. We now have a platform that we can use to test drugs on a ‘personalised medicine’ basis.

“Having developed and validated the model is the first crucial step, and in our ongoing collaborative work we will be working with others to better understand how the bone marrow works in healthy people, and what goes wrong when they have blood diseases.”

Dr Psaila added: “We hope that this new technique will help accelerate the discovery and testing of new blood cancer treatments, getting improved drugs for our patients to clinical trials faster.”

A ‘cellular brake’ which could prevent lung cancer patients from developing a dangerous autoimmune response during treatment has been identified by scientists.

The finding, published in Nature Communications, is the first clue to the cause of autoimmune toxicity, in which patients develop dangerous additional conditions during immunotherapy treatment.

Immunotherapy works by enabling the body’s immune cells (T cells) to engage with and kill tumour cells. They do this by suppressing proteins called immune checkpoints. These exist to prevent an immune response from being so strong that it destroys healthy cells in the body.

Autoimmune toxicity, which includes conditions such as pneumonitis, or inflammation of the lungs, can affect lung cancer patients undergoing immunotherapy treatment. Pneumonitis is responsible for around 35 per cent of treatment-related deaths in lung cancer patients.

Given the increasing use of immunotherapy treatment against cancer, the management of these reactions has become a significant healthcare challenge. Most commonly, clinicians will recommend discontinuing the treatment and exploring other options.

Led by Professor Gary Middleton, the team, in the University’s Institute of Immunology and Immunotherapy pinpointed a specific biological response among patients who develop autoimmune toxicity. They found a ‘cellular brake’ – a protein which would normally limit the activity of the T cells – is missing or not functioning properly.

By identifying patients who lack this cellular brake, it may be possible to recognise patients at high risk of developing severe autoimmune complications.

Lead author Dr Akshay Patel said: “Immunotherapy is an extremely important weapon in cancer treatment and so identifying people who are at particular risk of developing these potentially life-threatening autoimmune conditions is key to weighing the risks and benefits of different treatments. It would enable clinicians to closely monitor high-risk patients, develop preventative strategies, or pursue alternative treatments altogether.”

The research was funded by Cancer Research UK and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre.

A new way in which cancer cells can repair DNA damage has been discovered by researchers at BHP founder-member the University of Birmingham.

These new findings shed new light on how cancer cells react to chemotherapy and radiotherapy, and also uncover a new way in which cancer can become resistant to particular treatments. These insights may enable clinicians to select different cancer treatments that can be more targeted to specific patients.

Repairing damage to DNA is vital for cells to remain healthy, and to prevent diseases like cancer from developing. Understanding how DNA repair works is crucial to better understand how cancer develops, and also how anti-cancer treatments like radiotherapy and chemotherapy can be used effectively to induce DNA damage that kill cancer cells.

In the study, published in Molecular Cell, a team of researchers in the University’s Institute of Cancer and Genomic Sciences pinpointed two proteins that had not previously been identified in the DNA repair process.

Professor Martin Higgs, Associate Professor for Genomics and Rare Disease in the Institute of Cancer and Genomic Sciences, explained: “This research has the potential to change how cancer patients are identified for treatment and also how they become resistant to different drugs, which will improve treatment efficiency as well as patient outcomes.”

Called SETD1A and BOD1L, these proteins modify other proteins called histones which are bound to DNA. Removing these two proteins changes how DNA is repaired, and makes cancer cells more sensitive to radiotherapy. Loss of SETD1A and BOD1L also makes cancer cells resistant to certain anti-cancer drugs called PARP inhibitors.

Lead author Associate Professor Martin Higgs explained: “This is the first time that these genes have been directly linked to DNA repair in cancer. This research has the potential to change how cancer patients are identified for treatment and also how they become resistant to different drugs, which will improve treatment efficiency as well as patient outcomes.”

The team hopes the work could eventually also lead to new inhibitors being developed that would allow clinicians to re-sensitise cancers that have become resistant to certain therapies.

The research was funded by the Medical Research Council, Cancer Research UK, and the Wellcome Trust.