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14 new CRUK Oxford Centre Development Fund Awardees

The CRUK Oxford Centre are pleased to announce the 14 projects that have been selected to receive pump-priming funds. This unique scheme aims to support collaborative projects in cancer research which are a key area of activity for the Centre.

Please see a summary of the awardees and their projects below.

Tom Agnew, Sir William Dunn School of Pathology

ARH3 as a potential new biomarker in breast, ovarian and pancreatic and prostate cancer

To protect the genome from damage, organisms have evolved a cellular defence mechanism termed the DNA damage response. Exploiting DDR pathways to specifically target and kill cancer cells has become an attractive therapeutic avenue of cancer research. This is exemplified by the synthetic lethal interaction between PARP inhibition and BRCA1 or BRCA2-deficient tumours. PARP inhibitor drug resistance is a major issue for treating these cancers. This project will investigate the ARH3 enzyme as a target of reversing this resistance.

 

Elizabeth Mann et al., The Kennedy Institute of Rheumatology, NDORMS

Ex vivo phenotyping of Th17 cells from colorectal cancer patients

Although the immune system is critical in protecting against cancer development, inflammation can worsen disease. Impairing Th17 cells, a subset of CD4+ T cells, reduces tumour burden in mouse models of colorectal cancer (CRC) indicating that Th17 signalling may have novel biomarker and/or therapeutic utility. This project will investigate if Th17 cells are different in number and phenotype in clinically-relevant subclasses of CRC tumours – thus making them potential biomarkers

 

Kourosh Honarmand Ebrahimi & James McCullagh, Department of Chemistry, Chemistry Research Laboratory

Metabolomics investigation of an emerging immunometabolic pathway linking viral infection and inflammation to cancer

The activity of the antiviral enzyme radical S-adenosylmethionine (SAM) containing domain 2 (RSAD2) (also known as viperin) plays a key immunometabolic role in supporting immune function to fight a wide range of viruses. In tumour microenvironment, this activity could support tumorigenesis and tumour development via different mechanisms. In this project, the team will use a variety of analytical methods, including metabolomics and 13C tracer studies, to investigate how the immunometabolic function of RSAD2 supports cancer cell proliferation.

 

Linna Zhou, The Ludwig Institute & Department of Chemistry

Engineered gastrointestinal tissues to investigate the influence of enteric neurons in cancer progression

It has been increasingly recognised that the interactions between neurons and cancer cells, and neurons and immune cells, are important in cancer initiation, progression and metastasis. This project will use an engineering approach to generate 3D GI tissues with naturalistic cellular architecture to recapitulate the interactions of enteric neurons, immune cells and epithelial cells during cancer development. This is to assess how cancer cells migrate along neurons and how neuro-immune interactions shape the tumour microenvironment to facilitate the growth and migration of cancer cells.

 

Mariolina Salio & Graham Collins, Human Immunology Unit & Department of Haematology, Oxford University Hospitals

Immune microenvironment signatures predictive of response in patients with classical Hodgkin Lymphoma treated with checkpoint inhibitors

A major goal in the treatment of classical Hodgkin Lymphoma (cHL) is to reduce the burden of chemotherapy and radiotherapy with its associated short- and long-term toxicities, whilst maintaining high rates of cure. PD1/PD-L1 inhibitors are associated with high response rates. In solid tumours, the mechanism of action of PD1/PD-L1 inhibitors is believed to be mediated by enhanced activation of tumour specific CD8+ T cells. In cHL few CD8+ T cells are present in the tumour microenvironment, so the mechanism of action of PD1 inhibitors in this disease is still unclear. This project will investigate changes in the tumour microenvironment in biopsy material from patients with cHL treated with PD1/PD-L1 inhibitors, to identify signatures which might correlate with the therapeutic effect of these drugs.

 

Karthik Ramasamy & Ross Sadler, Department of Haematology, Oxford University Hospitals & Nuffield Department of Medicine

Post translational modification of free light chains as a biomarker for progression from monoclonal gammopathy of undetermined significance to myeloma

A pilot study to characterise post translational modifications of serum free light chains in both patients with MGUS and myeloma. A full summary of this project can be found here.

 

Monica Olcina et al., MRC Oxford Institute for Radiation Oncology, Department of Oncology

C5aR1 as a biomarker in ovarian cancer – Towards the development of radioligands for imaging and therapy of C5aR1 expressing tumours 

This project will assess C5aR1 as a biomarker to support the development of radioligands for molecular imaging and therapy of C5aR1 expressing tumours. Emerging evidence indicates that C5aR1 signalling stimulates ovarian cancer growth through regulation of oncogenic PI3K/AKT signalling. This project is investigating C5aR1 expression in a range of human ovarian cancer and healthy tissues and will also establish C5aR1 overexpression and knockdown cell lines to be used as tools in the development of radioligands (synthesised by collaborators). In the future, these radioligands will be preclinically tested for selective targeting and visualisation of C5aR1-expressing tumours – with ultimate testing in future clinical trials.

 

Ricardo Fernandes, Nuffield Department of Medicine

Development of a new approach to target FLT3 signalling in AML

This project will develop protein molecules to reduce signalling by the FLT3 receptor in myeloid cells. Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, and approximately a third of patients with AML present a heterogeneous group of activating FLT3 gene mutations. Enhanced FLT3 activity contributes to abnormal proliferation and differentiation of myeloid cells. Despite representing an attractive therapeutic target, small molecule inhibitors of FLT3 have achieved mixed results in clinical trials, partly driven by the diversity of FLT3 gene mutations and escape variants. This project will investigate a new approach for suppressing receptor signalling.

 

Simon Carr & Wojciech Barczak, Department of Oncology

Tumour specific neo-antigens derived from the non-coding genome

Cancers use a diverse array of mechanisms to evade the immune system such as down-regulating immune checkpoint pathways, and the development of therapeutic antibodies targeting immune checkpoints (such as anti-PD1 and CTLA4) represents one of the most important breakthroughs in cancer therapy. This project will look at the contribution of the non-coding genome to the tumour antigen landscape. It will use a novel method to manipulate the antigen landscape on tumour cells, by blocking PRMT5 activity, which we have shown to be important in regulating the expression of a proportion of the non-coding genome.

 

Andrew Blackford, Department of Oncology

Characterising short linear peptide motifs in tumour suppressor proteins 

Some tumour suppressor genes that are most commonly found to be mutated in patients with a hereditary predisposition to cancer are involved in repairing DNA damage in cells. However, we still do not understand exactly how many DNA repair proteins work at the molecular level, how drug resistance can develop in DNA repair-deficient tumours, nor why mutations in the intrinsically disordered regions of these proteins outside their known protein domains can predispose to cancer.

There is thus an urgent need to do more basic research into how DNA repair proteins function at the molecular level in order to understand potential drug resistance mechanisms as well as identify additional drug targets when resistance to radiotherapy and chemotherapy develops. The aim of this project is to identify novel protein interactors for the highly evolutionarily conserved but as-yet uncharacterized short linear peptide motifs in DNA repair proteins.

 

Thomas Lanyon-Hogg, Department of Pharmacology

Development of novel Hedgehog acyltransferase inhibitors from HTS hits to lead series

Hedgehog (Hh) signalling drives growth and is activated in several cancers. Hedgehog acyltransferase (HHAT) activity is required for Hh signalling, making HHAT an attractive target for inhibition. This project will build on the labs existing success in order to develop the most potent HHAT inhibitors to-date.

 

Val Macaulay, Ian Mills & Jack Mills, Department of Oncology & Nuffield Department of Surgical Sciences

Investigating nuclear IGF-1R function in clinical prostate cancers

 Insulin-like growth factors (IGFs) play key roles in prostate cancer biology. Type 1 IGF receptors (IGF-1Rs) are up-regulated in primary cancer and associated with lethal castrate-resistant prostate cancer (CRPC). This project aims to understand how nuclear IGF-1R regulates expression of genes contributing to cancer cell growth, androgen response and therapy resistance in vivo.

 

Wayne Paes et al., Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine

Empirical determination of molecular biomarkers for precision-based immunotherapy in colorectal cancer

 Immune checkpoint inhibitors (ICIs) are only efficacious in ~15% of CRC patients while tumours in ~85% of patients remain innately resistant to ICI therapy. This pilot study aims to identify and correlate novel biomarkers in Immune Checkpoint Inhibitor (ICI)-sensitive and ICI-refractory colorectal cancer subsets at multiple levels. Characterisation of subsets will allow for identification of which are most responsive to ICIs and identify new potential therapeutic targets for those that are not.

 

Shijie Cai et al., Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine

Identification of small molecule inhibitors and synthetic lethality for GTP cyclohydrolase in triple-negative breast cancer

Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancer, with over 8000 cases diagnosed every year in the UK and estimated 1.7 million new cases worldwide. TNBC differs from other types of breast cancer in that they grow and spread faster. Chemotherapy is still the mainstay therapeutic option; however, patients suffer a high rate of distant recurrence and death. Thus, there is an unmet need to develop new small molecule inhibitors for TNBC therapy. GTPCH is a recently identified protein that drives TNBC growth. This project will identify small molecule inhibitors and synthetic lethal genes for GTPCH and enable the researchers to develop new inhibitors targeting TNBC.

Oxford success at the early detection sandpit on pancreatic cancer

Pancreatic cancer is a devastating disease with low survival rates that have hardly improved in the last 40 years. These cancers are very challenging to treat, in part due to their frequently late diagnosis when the cancer is already advanced.

To address this need for earlier detection, Cancer Research UK, Pancreatic Cancer UK and the Engineering and Physical Sciences Research Council convened a 3-day virtual workshop in November 2020. Multidisciplinary teams worked together to generate innovative research ideas for detecting pancreatic cancer earlier. At the end of the workshop, the teams pitched their ideas to receive seed funding for feasibility testing from a Cancer Research UK Early Detection Innovation Award. Two successful teams involved Oxford researchers.

Team ReTHOMS: Real-time high-sensitivity optrode metabolic sensor for pancreatic cyst fluids

Team ‘ReTHOMS’ includes Oxford’s Professor Eric O’Neill (Department of Oncology) who is working with Dr Paolo Bertoncello (Swansea University), Dr David Chang (University of Glasgow) and Dr George Gordon (University of Nottingham). The team aims to develop a new sensor device to detect malignant transformation in people with pancreatic cysts, a condition that puts them at higher risk of pancreatic cancer.

Pancreatic cysts are fluid-filled sacs on or in the pancreas that are mostly benign. However, 2-3% are precancerous and can develop into pancreatic cancer. Cysts are often identified incidentally and are then monitored for malignant transformation using either clinical imaging or analysis of the cyst fluid for cancer biomarkers such as mucins. Despite this surveillance regime, early cancers are still being missed since these methods have limited sensitivity and specificity.

To improve the early detection of malignant cyst transformation, the team aims to develop real-time and highly sensitive detection of an expanded range of cancer biomarkers. In addition to mucin, raised cellular levels of the chemical hydrogen peroxide are associated with cancer. So-called optrode technology will be used to detect hydrogen peroxide and mucin in cyst fluid. Optrodes are optical sensor devices that detect light emitted as a result of an electrochemical reaction with the biomarkers being analysed.

During this short project, the team will build the optrode device for measuring hydrogen peroxide and mucin, and undertake technical and biological validation. The longer-term aim of this research is to detect pancreatic cancer earlier by screening pancreatic cyst fluid at the point-of-care and determining further action based on the risk of cancer.

Team EDPAN: Earlier detection of pancreatic cancer through personalised assessment of risk combined with non-invasive infrared spectroscopy

Oxford’s Dr Pui San Tan (Nuffield Department of Primary Care Health Sciences) will work as part of team EDPAN with Dr Pilar Acedo Nunez (University College London), Dr Aida Santaolalla (King’s College London), Dr Paul Brennan (University of Edinburgh), Dr Lucy Oldfield (University of Liverpool), Dr Andrew Kunzmann (Queen’s University Belfast) and Dr Mohammad Golbabaee (University of Bath). This team aims to identify individuals at higher risk of pancreatic cancer for further diagnostic screening.

One of the reasons that pancreatic cancer is often diagnosed late is that symptoms are non-specific and cannot discriminate those that require investigation for pancreatic cancer. Team EDPAN will develop an approach for personalised risk stratification to identify individuals at higher risk that would benefit from more in-depth screening for pancreatic cancer.

During the project, the team will make use of existing cohorts for pancreatic cancer (ADEPTS (UCL) and PanDIA (Liverpool)) and larger cohorts for epidemiology research (UK Biobank, AMORIS). They will combine clinical and demographic information with analysis of serum and urine samples using a technique called infrared spectroscopy. They will also evaluate changes in immune components. These approaches aim to identify individuals at high-risk of pancreatic cancer and investigate whether addition of infrared spectroscopy data and immune analysis improves the accuracy of the risk prediction model.

Early Detection Award for research into the clinical application of single cell genomics

Myelodysplastic syndromes (MDS) are a group of blood cancers in which the bone marrow fails to make normal levels of blood cells. MDS can be broadly classified into two major groups: high-risk MDS, in which patients progress to acute myeloid leukaemia with a very poor survival rate; and low-risk MDS, in which the disease is less aggressive but patients still suffer from a huge burden of symptoms, often the result of anaemia.

There are a number of exciting new targeted treatment options for low-risk MDS. However, these do not work in all patients and, particularly given the high economic cost of newer treatments, current biomarkers are not sufficiently predictive of treatment response. There is a need to more precisely categorise MDS to predict the disease trajectory and the response to therapy so that the most effective treatment can be given to each patient.

Large investments in sequencing technology in clinical laboratory services are enabling precision medicine in certain cancers and revolutionising patient care. Dr Onima Chowdhury, MRC Clinical Academic Research Fellow and Consultant Haematologist (MRC Weatherall Institute of Molecular Medicine and Oxford University Hospitals) is working with Professor Adam Mead, Dr Supat Thongjuea and Dr Lynn Quek at the MRC WIMM to explore the use of single-cell genomics in the clinical diagnosis and management of MDS. Funded by a Cancer Research UK Early Detection and Diagnosis Primer Award, the team will seek to develop a simple, clinically applicable processing and analysis pipeline, as well as identifying biomarkers that correlate and can perhaps supersede current diagnostic modalities.

Long-term, the team hope that this approach will be able to improve outcomes of patients through improved diagnosis, risk prediction and targeted treatment in MDS and other haematological malignancies.

New funding for early diagnosis research using platelets

It is known that the earlier a cancer is detected, the more likely a cancer patient is to have better outcomes. One of the challenges for achieving early detection is to develop a minimally invasive test to detect the signs of early cancer in the body.

Because blood tests are simple to carry out in the clinic, a lot of effort has been focused on detecting molecules released from cancer cells in blood samples – so-called ‘liquid biopsies’. However, the majority of techniques that are used currently have a low sensitivity for early-stage cancers, due to low levels of cancer cell-derived molecules being present in blood plasma.

Dr Bethan Psaila, Cancer Research UK (CRUK) Advanced Clinician Scientist, Group Leader at the Medical Research Council Weatherall Institute of Molecular Medicine (MRC WIMM) and principal investigator at the Radcliffe Department of Medicine at Oxford University, is pioneering an approach that might be able to enrich for cancer-derived molecules in the blood. Working with Professor Chris Gregory (University of Edinburgh), Professor Paul Rees (University of Swansea) and Dr Henkjan Gersen (University of Bristol), Beth is leading a multi-disciplinary team that brings together cancer cell biologists, and imaging and engineering expertise to explore the use of platelets for early cancer diagnosis.

Platelets perfuse tumours and take up cancer cell-derived biomolecules. Isolating platelets from the blood and analysing their contents will hopefully be a more sensitive method for detecting cancer-specific molecules in the blood.

In this newly funded project, the team will use state-of-the-art pre-clinical models as well as samples from patients with colorectal cancer, pancreatic cancer and oesophageal cancer as exemplar cancers to assess the utility of ‘tumour-educated’ platelets (TEPs) for early cancer diagnosis. They will use detailed imaging and biomechanical techniques to assess whether TEPs can be reliably distinguished from platelets in healthy people or those with non-malignant disorders.

This multi-institutional project is funded by a Cancer Research UK Early Detection and Diagnosis Project Award and builds on a successful CRUK Innovation Award the team received after a workshop on liquid biopsy technologies in 2018. The ~£650,000 award will run for four years and will support two DPhil studentships, a postdoctoral research scientist and a research assistant.

Novel imaging device enters first round of development funding programme

Proton-beam-therapy (PBT) is becoming increasingly important for treating cancer, with projected increases of up to 50% more patients per year being treated with the technology in the UK and worldwide by 2025.

Although the precision of PBT has many advantages over traditional radiotherapy, there some uncertainty over the range of delivery the beam provides. There is risk of potential overdose to normal tissues or underdose to tumour, resulting in reduced tumour-control and long-term side-effects due to treatment of healthy tissue. This can be detrimental to patients and a burden on healthcare systems if side-effects become apparent later in a patient’s life.

Therefore, a method to verify the range of treatment beams when using PBT on patients is crucial to increase the treatment accuracy. Dr Anna Vella, Postdoctoral with the Radiation Therapy Medical Physics Group, led by Prof. Frank Van Den Heuvel, at the University of Oxford’s Department of Oncology, is investigating the efficacy of a device with this purpose.

Anna is leading CAPULET (Coded Aperture Prompt-gamma Ultra-Light imaging detector), an imaging device for quality assurance assessment of radiotherapy plan efficacy, designed for daily use in clinical practice. CAPULET could be installed onto a variety of PBT devices, and used to verify and fine-tune the dose between fractions in particle-beam radiotherapy. It does this through collecting 3D images of the particle beam penetrating soft-tissue, with the ultimate goal to fine-tune planning doses and improving the efficacy of the overall radiotherapy treatment.

This novel and unique technology is faster & more compact than current devices, increases the field-of-view, and improves the signal-to-noise ratio. The impact on patients will be to improve cancer-control, fewer complications, and improved quality-of-life following treatment.

CAPULET has recently been selected as one of 35 projects in the Pre-Development Phase of the Alderley Park Oncology Development Programme – a national programme designed to develop and progress start-up oncology projects. Funded by Innovate UK and Cancer Research UK. It will now be work-shopped, and potentially be chosen to join the full development programme with grant funding.

Proof-of-concept experiments will be performed in collaboration with the CRUK-funded ART-NET. The long-term plan of CAPULET is to develop a large-area detector to fully image the beam delivery range within lungs, liver, H&N and other large sites in the human body to overcome limited field-of-view found in other existing devices on the market.

Funding to improve childhood, teenage and young adult cancer detection

Cancer is the commonest cause of death among children and young people in the UK and is associated with significant long-term morbidity. Unfortunately, the UK lags behind other high-income countries in the time it takes to diagnose childhood, teenage and young adult (TYA) cancer and this delay worsens patient outcomes.

One of the challenges in diagnosing childhood and TYA cancer is its relative rarity and non-specific presentation, and awareness campaigns have been run in an effort to improve recognition of cancer signs among health professionals. Although this resulted in improvements for certain types of cancers in children and TYA, the national time-to-diagnosis targets have still not been reached in all cancers for all age groups.

Dr Defne Saatci and Professor Julia Hippisley-Cox (Nuffield Department of Primary Care Health Sciences) have successfully applied for a Cancer Research UK Early Detection and Diagnosis Project Award to accelerate diagnosis of childhood and TYA cancer. They will use the QResearch database, the UK’s largest GP electronic health record database, covering 20% of the UK population and linked to national cancer, hospital and mortality registries. QResearch data will be explored to identify the early symptoms and signs associated with a subsequent diagnosis of the commonest childhood and TYA cancers (acute lymphoblastic leukaemia, lymphomas and central nervous system tumours) and this information will be used to develop a risk prediction tool for GP use.

By increasing the understanding about the clinical features associated with childhood and TYA cancers and developing this risk prediction tool for use in primary care, this study aims to make significant advancements in childhood and TYA cancer diagnosis and outcomes.

If you are an Oxford-based researcher thinking of applying for external early detection funding, please get in touch with the OxCODE Scientific Coordinator who can help to coordinate your application.

 

New Oxford spin-out Singula Bio launches

Singula Bio is a bold new seed-stage biotechnology company spun out of Oxford University. It aims to become a world leader in developing neoantigen-based individualised cell therapies to use against difficult-to-treat solid malignancies such as ovarian cancer.

This patient-centred approach will pioneer immunological, medical, surgical and computational technologies to generate selective therapies that eliminate cancer, and the ultimate hope is to achieve long-term, high-quality disease-free survival for cancer patients.

Singula Bio was co-founded by Professors Ahmed Ahmed, Enzo Cerundolo and Enda McVeigh from the Nuffield Department of Women’s & Reproductive Health at Oxford University. It is supported by Oxford University Innovation (OUI), the University’s research commercialisation company, and it has secured generous seed-stage investment from IIU Nominees Limited to pursue its goals. Singula Bio is a landmark for OUI as it is the 250th OUI-supported venture to have passed through the office since it opened its doors in 1987.

Motivated by their many patients (and laboratory funding from charities Ovarian Cancer Action and Cancer Research UK) Profs Ahmed and Cerundolo were inspired to improve an individual’s gruelling experience of cancer and to lessen their suffering of other treatments. Together, they have an enormous knowledge in cancer medicine, cancer immunology, cell and molecular biology, and computational biology which has enabled them to design patient-specific cancer cell therapies that harness the power of the patient’s own immune system to fight cancer.

In a tumour, cancer cells carry mutations that appear foreign to a patient’s body and, therefore, their immune system reacts to these mutations. One strong form of an immune reaction is through generating mutation-specific cells called “T cells”.

Prof Ahmed, Professor of Gynaecological Oncology at the Nuffield Department of Women’s & Reproductive Health, Oxford University, said:

“A key feature of cancer cells is the preponderance of genetic aberrations in their DNA. These aberrations can make proteins appear foreign to our body’s immune system which then develops immune cells (T cells) to fight cancer cells. Thanks to years of research and technology development we now know how to identify relevant tumour-specific T cells to grow them outside the body and deliver them back to patients to fight cancer cells.”

Studying viral genetics to aid liver cancer early detection

Chronic Hepatitis C virus (HCV) infection causes liver damage and is a significant risk factor for liver cancer. There are now cures available for chronic HCV infection and the World Health Organisation has set a target to eliminate HCV by 2030. However, although curing HCV reduces the risk of liver cancer, individuals with a history of chronic HCV infection remain at higher risk.

There are multiple types of HCV that differ in their genetic sequences. Previous research has established that not all HCV genotypes present the same level of risk for liver cancer. The next step is to discover which particular viral genetic motifs are most associated with liver cancer so the HCV-infected individuals who are at the highest risk of liver cancer can be identified. This will enable more targeted surveillance to detect liver cancer earlier when treatment is more likely to be successful.

Professor Ellie Barnes and Dr Azim Ansari (Nuffield Department of Medicine) have been awarded funding as part of a wider Wellcome Trust Collaborative Award led by Professor Graham Foster (Queen Mary’s University, London) to study anti-viral drug resistance and long-term effects of HCV in Pakistan. HCV infection is highly prevalent in Pakistan with up to 20% of the population infected in hotspot regions.

A cohort of ~500 individuals with HCV-associated liver cancer will be recruited and samples will be collected for viral whole genome sequencing. The Oxford team will then analyse these sequences, comparing to people with HCV infection but not cancer, to identify any genetic patterns that are linked to cancer.

This work complements the recently launched Cancer Research UK-funded DeLIVER programme which, among other features, will study host and viral genetics in a cohort of individuals with HCV and liver cancer in the UK.

Christina Ye awarded CRUK pre-doctoral fellowship

Immune related toxicity is a common side effect of treatment with Immune Checkpoint Blockers for cancer – but the degree to which the development of these side effects is related to overall oncological outcome is unclear. As an Academic Foundation Programme Trainee within OUCAGS (https://www.oucags.ox.ac.uk), I had a four month block of time to work in a lab to gain experience of research. I worked with Dr Benjamin Fairfax’s group in the WIMM/Department of Oncology to explore the relationship between immune toxicity and clinical outcomes. Working with other members of the group, and Dr Anna-Olsson Brown in Liverpool, we found that patients who developed immune related toxicity appeared to have better long-term clinical outcomes including overall survival. Indeed, we found the development of toxicity was a key predictor of the cancer responding to treatment. This work is currently in-press in the British Journal of Cancer.

This period of time in the lab stimulated my interest in research and helped in my decision to apply for an Academic Clinical Fellowship in Dermatology. I was successful in this and I have a further nine months of protected research built into my training this year, which I again plan to spend working in Ben’s group. As a trainee dermatologist I am particularly intrigued by the rash patients frequently develop when they first receive immunotherapy. There is evidence to suggest that another side effect of immunotherapy, colitis, is secondary to the activation of resident memory T cells. Conversely, when you look at the gene expression in CD8 T cells after treatment with checkpoint blockers you can see up-regulation of genes involved in skin trafficking. I will explore whether this rash is indicative of T cell trafficking to the skin, or activation of resident memory T cells, or something completely separate.

Cancer Research UK awards biannual pre-doctoral research bursaries, aimed at providing ‘short term funding to allow clinicians and other health professionals to get involved in research projects early in their career’. Ben encouraged me to apply to this CRUK scheme to further explore the mechanistic basis of the rash in immunotherapy and I am very grateful to have been awarded this funding. Personally I am hoping to gain training in immunological techniques and bioinformatic analysis during this period, and I hope the results we generate will provide further insights into the cells cancer immunotherapy affects and how it works.

Funding boost for OxPLoreD early detection study

OxPLoreD is an observational cohort study sponsored by Johnson and Johnson that will recruit 1650 patients from across the UK with pre-cancerous lymphoproliferative disorders. These conditions include monoclonal B-cell lymphocytosis and monoclonal gammopathy of unknown significance that put individuals at higher risk of developing the blood cancers chronic lymphocytic leukaemia and multiple myeloma respectively.

The aim of the study is to look for new ways to find and treat blood cancer sooner by identifying clinical, genomic and immunological predictive markers of progression from these pre-cancerous conditions to malignant disease. The study will also explore the possibility of a future early intervention trial for the subgroup of patients at highest risk of progression.

OxPLoreD is one of the seven clinical trials that have received an £8m funding boost from UK Research and Innovation (UKRI) and will work in partnership with Genomics England. The funding will speed up the adoption of whole genome sequencing in the study of cancer. Genetic analysis is a critical tool that can allow clinicians to select the most appropriate treatments for each patient. In the OxPLoreD study, genetic analysis might be able to identify individuals at highest risk of disease progression that would benefit from earlier treatment. In the longer term this may also enable the identification of those people who would benefit from certain types of treatment.

Alison Cave, UKRI challenge director says:

“Research tells us that one-in-two people in the UK population will get cancer. That stark statistic shows just how important it is for us to seek new treatments. The use of genetic analysis opens new possibilities in our drive to beat cancer. The projects for which we have announced funding today are exciting pointers to future diagnosis and precision treatments”

The funding has been delivered through UKRI’s Industrial Strategy Challenge Fund’s £210m data to early diagnosis and precision medicine (DEDPM) programme. The challenge aims to combine research data and evidence from the NHS to create new and improved ways of identifying disease and treatment pathways.

Prof. Sir Mark Caulfield, Chief Scientist at Genomics England says:

“The 100,000 Genomes Project, Genomics England has analysed the genomes of over 17,000 cancer participants and this suggests that up to half have revealed mutations of potential clinical significance. The DEDPM programme is a major opportunity to expand the application of whole genome sequencing into clinical trials involving cancer where support from the ISCF is likely to deliver significant clinical benefit”

For more information about the other trials funded by this scheme, see the UK Research and Innovation announcement.