Research is the cornerstone of our mission to beat blood cancers. We want to stop people dying from blood cancers, give patients a quality of life no different from if they were cancer-free and stop people from getting blood cancers in the first place.
To our scientists, this is natural: they are driven by the same mission as the charity and will not stop until it is achieved. And the investigators who we have just invested in are no exception. We have just committed £9m to support top-class research into leukaemia, lymphoma and myeloma.
We are also thrilled to support four doctors (‘clinical fellows’) and four enthusiastic postgraduate students to carry out exciting research projects and complete PhDs in leading LLR labs. These commitments will provide a strong foundation of research excellence for the long-term future and strengthen the ties between the lab and the clinic.
We have also made significant investments to support on-going clinical trials with some cutting-edge lab research. This intimate link between the laboratory and the clinic is extremely encouraging, as it ensures maximum information is gained from current clinical trials to which patients so generously commit. Patients benefit from this because clinical trials become more efficient by adapting on a continuing basis to emerging laboratory insights, further helping to personalise treatment. Researchers also benefit because valuable blood and tissue samples from patients, properly anonymised, are available for future research use.
It is increasingly clear that rapid advances in technology are offering new opportunities to researchers, allowing them to ask questions that were previously impossible. Technology drives research as much as the other way round. This is reflected in the projects in the current round – cheap and astonishingly quick DNA sequencing, exquisitely sensitive imaging and scanning of entire gene and protein networks will allow collection of data on an incredible scale. The consequence of ‘big data’ is ‘big analysis’, and our scientists will need to exploit ever-better computer power. Many labs now house or partner with staff whose specialty is handling and making sense of large datasets.
So what are these new projects?
Inspiring new treatments & better care
Professor Paul Murray at the University of Birmingham will use his five-year programme to study how Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) cells communicate with their surroundings to sustain survival and cell growth. Professor Jacqueline Boultwood’s five-year programme at the University of Oxford will focus on myelodysplastic syndromes – a group of pre-cancerous conditions that commonly develop into acute myeloid leukaemia (AML). She will use the latest DNA technologies to study how the activity of tens of thousands of genes are affected in abnormal cells, as well as the trail of genetic faults that arise as the disease evolves. Professor Tatjana Stankovic’s clinical fellow at the University of Birmingham, who will identify faults that drug resistant chronic lymphocytic leukaemia cells carry. These projects aim to discover how these signals can be disrupted to treat these diseases, and in Prof Boultwood’s case, to prevent leukaemia from even starting. Prof Murray has, up until now, focussed on HL, but the inclusion of DLBCL is a nice example of how research in one blood cancer can resourcefully translate into benefits for another.
Professor Ronjon Chakraverty’s clinical fellow at University College London and Dr Stephen Man’s three-year project at Cardiff University are based on a similar premise: that a certain class of immune cells, called ‘T-cells’, can be engineered to home in and destroy cancer cells in an extraordinarily selective way. On a similar theme, but moving more towards improving current treatment, Professor Tim Illidge at the University of Manchester has a new three-year project to investigate how therapy that harnesses the power of the immune system can be best combined with traditional chemotherapy to provide the most effective and long-lasting anti-cancer effects in several lymphomas.
To make existing treatments for childhood acute lymphoblastic leukaemia (ALL) kinder, Professor Caroline Austin’s student at Newcastle University will investigate whether blocking certain biochemical processes can preserve or even enhance the current treatment, whilst reducing the type of genetic damage that could lead to later leukaemias. Approximately 10 percent of AML cases are caused by prior cancer therapy. Dr Julie Irving at Newcastle University will support an international clinical trial that’s testing new therapies for children with ALL who responded to initial treatment but whose cancer then came back – known as ‘relapse’.
And like Dr Irving, there are those doing bringing discoveries to the clinic. Dr Chris Fox at the University of Nottingham will run a clinical trial through our pioneering Trials Acceleration Programme to test the best drug combinations for difficult-to-treat or relapsed primary central nervous system lymphoma – a rare but aggressive non-Hodgkin lymphoma (NHL) with poor clinical outcome. Dr Alistair Reid, a clinician scientist at Imperial College London is pioneering an exquisitely sensitive DNA-based test that will be better able to detect and monitor rogue cells to see whether it’s safe for some chronic myeloid leukaemia (CML) patients to discontinue the drug imatinib (trade name Glivec). Dr Gladstone Austin Amos Burke, Addenbrooke’s Hospital Cambridge, will use biological samples from a clinical trial in several childhood NHLs to detect whether trace molecules associated with cancerous cells can predict clinical outcome.
Driving Smarter, Faster Diagnosis
Professor David Westhead at the University of Leeds has a three-year project to use some extremely powerful and complex computational techniques to look at the DNA code, the scale of gene activity and the suite of proteins present in many blood cancer cells. He will then combine this information with data on clinical outcomes. This will allow doctors to better identify the type of disease a patient has, regardless of traditional classifications, and predict its likely progression. Dr Simon Rule’s clinical trial at Derriford Hospital, Plymouth aims to segregate, at diagnosis, mantle cell lymphoma patients who have aggressive disease requiring immediate treatment from those who have inactive disease who may never need treatment.
We know that knowledge of the cancer biology helps to sort patients by the specific type of disease at the outset, better informing clinical decisions and getting the right treatment to the patient sooner. In fact, now that we have the power to discriminate cancers by the genetic faults that drive them and their characteristic molecular signatures, as these projects are doing, it is perhaps now time to re-think how we categorise these diseases – in terms of how we treat the disease, for instance, a CML in one person might actually be more similar to someone else’s ALL than to another person’s CML.
Revealing How Blood Cancer Works
As has been shown above, understanding the basic biology of blood cancers stimulates research that can ultimately translate to patient benefit.
A suite of newly funded projects focus on identifying faulty molecules and working out their roles in various blood cancers. This can offer new targets at which to aim precision drugs, as will be done by Professor Ken Mills at Queen's University Belfast in myelodysplastic syndromes, Professor Alison Banham's team at the University of Oxford in ‘B-cell’ cancers, Dr Gina Doody at the University of Leeds in Waldenström macroglobulinemia (a rare NHL), and Professor David Grimwade's programme at King's College London in acute promyelocytic leukaemia and therapy-related leukaemias.
In a comprehensive example of this approach, Dr Graham Taylor’s clinical fellow at Imperial College London will characterise the entire series of genetic changes that occur from the point at which cells are infected by the human T-lymphotropic virus type 1 to the emergence of adult T-cell leukaemia-lymphoma. Dr Katrin Ottersbach’s Bennett Fellowship extension at the University of Cambridge will tease out in which immature blood cells the critical genetic events occur that lead to childhood leukaemia. Similar to Prof Westhead’s molecular-centric approach, Professor Ewan Cameron's group at the University of Glasgow will study a family of proteins – called ‘RUNX’ – that go awry in many types of blood cancer, meaning a wide range of traditionally distinct cancers could be targeted.
Knowledge of faulty molecules can also allow researchers to detect ‘markers’ of disease progression or response to drugs. Taking this approach, Dr Surinder Sahota’s three-year project on multiple myeloma at the University of Southampton will exploit a truly cutting-edge DNA scanning technique that reads DNA sequences from single cells, and Professor Tessa Holyoake’s student at the University of Glasgow will use high-powered computational analyses to identify abnormal molecular fingerprints in CML.
To exploit genetic techniques further, Dr Jim Allan at Newcastle will use his five-year programme to scan the DNA codes of hundreds of people with and without AML to predict the risk of developing a blood cancer and then the risk of disease relapse after successful treatment. At the same time, his team will develop treatment strategies, providing an integrated approach to personalised patient care.
But the function of normal cells can be illuminating too. Dr Martin Turner at the Babraham Institute, Cambridge has a two-year project to study biochemical signals within normal immature immune cells that regulate proper cell division, so that we can better understand how this process goes wrong in many blood cancers. Professor Lesley Forrester’s three-year project at the University of Edinburgh will find protein flags on the surface of normal blood stem cells and Dr Marella de Bruijn’s six-month project at the University of Oxford will uncover the genetic drivers of normal blood stem cell generation, both with a long-term goal that these could be grown in the laboratory and given back to a blood cancer patient to replenish normal blood function. In a similar vein, Professor Claus Nerlov’s student at the University of Oxford and Professor Tony Green’s clinical fellow at the University of Cambridge will look at changes in blood stem cells and their surroundings during leukaemia development, which may in the future help to restore normal blood stem cell function.
As I hope I’ve been able to convey, we’re very excited about the potential these projects have for real patient benefit. Thank you to all who have supported us – without you, none of this would be possible.