For more than three decades, the University of Birmingham has been at the forefront of cancer research and clinical trials. Ros Dodd reports on some of the transformational advances in treatment pioneered here.
Four decades ago, only 17 per cent of children survived neuroblastoma, an aggressive cancer and the most common childhood tumour outside the brain. Today, 64 per cent are treated successfully.
It’s a great improvement – but still not good enough, says Pamela Kearns, Professor of Clinical Paediatric Oncology and Director of Birmingham’s Cancer Research UK Clinical Trials Unit (CRCTU), set up more than 30 years ago and now one of the largest cancer trials units in the UK.
It is why the CRCTU is constantly conducting pioneering trials such as BEACON-neuroblastoma, a recently launched international multi-arm trial to see if a drug licensed for use on adults, called Avastin (bevacizumab), can help children with this type of cancer by targeting the tumour’s blood supply.
‘There is good biological evidence to suggest Avastin will be useful in treating children,’ she explains. ‘This is a new way of treating children with the disease across Europe – we are opening up the trial to six other countries – and we will modify it as new treatments become available. So it’s a rolling programme.
‘The importance of trials like this is that up until the last few years, children really didn’t have access to novel therapies. What we need to do is find a way of rapidly accessing drugs to see what works and what doesn’t, and that’s what this trial does. It may not be the primary interest of the pharmaceutical companies, but it’s in the interests of the children.’
Since 2012, the CRCTU has co-ordinated the national portfolio of Children’s Cancer Trials in 21 centres across the UK and Ireland, including Birmingham Children’s Hospital, bringing cutting-edge science from the lab to the bedside. More than 60 per cent of children with cancer can enter a clinical trial at diagnosis.
Happily, cancer in children is rare. Among adults, however, the disease is now the world’s biggest killer. By 2020, it is predicted that nearly half the UK population (47 per cent) will develop cancer during their lifetime – with almost a quarter of people dying from it.
The statistics would be grimmer still if it wasn’t for the breakthroughs made at the University. A notable example is breast cancer: research conducted in Birmingham has reduced deaths from the disease nationally by more than 30 per cent.
In 2010, Birmingham became Cancer Research UK’s first ‘super cancer centre’, bringing together world-class research and providing more than £8 million funding each year.
Its lofty standing is in no small part thanks to the work done by Professor Alan Rickinson, who led the development of the Institute of Cancer Studies (now the School of Cancer Sciences) from 1983 until 2001, overseeing its expansion from a small, non-clinical research department into a large research institute integrating basic work on cancer genetics, viral oncology and tumour immunology with translational studies in gene/immunotherapy and the activities of the CRCTU.
From 2001 until he officially retired last April, Alan concentrated on maintaining Birmingham’s reputation as an international centre of excellence for work on human tumour viruses, leading a large research group focused on the Epstein-Barr virus (EBV), a common human pathogen associated with several types of cancer, such as Hodgkin’s lymphoma and nasopharyngeal cancer.
Within the group, Dr Graham Taylor, Lecturer in Tumour Immunology, has carried out groundbreaking studies into the immune response to EBV that have led to the development of a vaccine to treat patients with such cancers by enhancing their immunity to particular EBV proteins present in the cancer cells.
The immune system has also played a key part in a major breakthrough in leukaemia. Researchers at the Leukaemia & Lymphoma Research Centre of Excellence, one of the UK’s largest transplant centres, have found that patients with leukaemia lack an immune response to a certain class of proteins – a response that could be restored through stem cell transplants. The discovery, announced in 2013, might even eventually lead to a vaccination against leukaemia for at-risk groups that are found to be lacking the necessary immune cells.
Work carried out by Professor Charlie Craddock, Director of the Centre for Clinical Haematology, has resulted in the development of an internationally competitive portfolio of early-phase clinical trials in allogeneic stem-cell transplantation and myeloid and lymphoid leukaemias, which allow rapid translation of scientific advances into clinical practice.
There have also been breakthroughs in breast cancer, which is the second leading cause of death among women in the UK. Much of Birmingham’s research has centred on the genetic make-up of the disease. Changes in genes such as BRCA1 mean that some women are at a very high risk of developing the disease, so the University is developing new ways to identify which changes in the gene are most likely to put health at risk. This not only helps to manage and improve treatment, but provides more insight into how the cancer develops.
Strides towards controlling bladder cancer have also been made at the University, which has one of the largest banks of bladder cancer tissue in the world to tackle the disease.
A study co-led by Nick James, Professor of Clinical Oncology, has found that adding radiotherapy to chemotherapy can nearly halve the chances of bladder cancer patients relapsing with the most lethal form of the disease, compared to patients given radiotherapy alone.
The success of the 2012 trial, led by the University and The Institute of Cancer Research (ICR), could mean fewer patients needing their bladders removed and provides a viable alternative for frailer patients who are too weak for surgery.
In another bladder cancer breakthrough (published in the British Journal of Cancer in November 2013), researchers carried out a study that showed a simple urine test could distinguish between aggressive, advanced forms of bladder cancer and less aggressive forms, helping to tailor and speed up treatment.
Birmingham has one of the largest programmes of clinical care in brain cancer within the UK. Its new Imaging Research Centre – located in the world-class Wellcome Trust Clinical Research Facility at Birmingham’s Children’s Hospital – focuses on using state-of-the-art scanning equipment to better identify the sort of tumour a child has before invasive surgery takes place. This means quicker diagnosis, helps to identify aggressive tumours and leads to faster treatment plans.
The growth of new blood vessels – or angiogenesis – is now widely accepted by the research community to be an essential component of tumour growth. Consequently, the blocking of angiogenesis is now a major area of research. Roy Bicknell, Professor of Functional Genomics, and his team are at the forefront of trying to understand the molecular basis of angiogenesis. Over the past few years they have identified several genes such as ‘magic roundabout’ and the endothelial cell specific molecules (ECSMs) that play an intimate role in the angiogenic process.
Immunology and immunotherapy are among the most promising prongs of attack in the race to cure cancer. Ben Willcox is Professor of Molecular Immunology based at the Birmingham Cancer Research Centre within the SCS.
‘We are studying a group of immune cells about which rather little is known: a type of T-cell called gamma delta T-cells,’ he explains. ‘We know they have the potential to recognise and kill cancer cells – and they have shown promise in clinical therapy trials – but, unlike conventional T-cells, we don’tunderstand what they are recognising. Part of the aim of our work is to understand the molecular basis of what they are recognising, with a view to exploiting them for novel immunotherapy approaches.’
The cancer breakthroughs made in Birmingham have already saved many lives. The work being done now is likely to lead to more life-extending therapies.
Professor Paul Moss, Head of the School of Cancer Sciences, says: ‘We are at the start of a revolution in cancer treatment that will see new techniques like gene therapy and immune therapy becoming routinely available to patients. This new generation of personalised treatment means we are the first generation that has the power to make cancer a condition that we manage effectively.’