NIHRDataInsights/HRCSData huggingface dataset:
Title: Oxford Cancer Research UK Centre (Non-Clinical Training Account)
Funder: Cancer Research UK

Abstract: Non-clinical training associated with the Oxford Cancer Research UK Centre: The Oxford Cancer Research Centre builds on the city's long history of groundbreaking scientific research, bringing together world-class scientists, doctors, nurses and radiotherapists to speed progress in beating cancer. The Centre is a partnership between Cancer Research UK, the University of Oxford and the Oxford University Hospitals NHS Trust. Researchers at the Centre are studying many different types of cancer. In particular, they are focusing on breast, skin, gastrointestinal and urological cancers, which covers bladder, prostate, kidney and testicular cancers. Radiotherapy research is a particular strength of the Oxford Centre, spearheaded by scientists at the Gray Institute for Radiation Oncology and Biology - created to be the largest group of doctors and scientists specialising in radiotherapy research in the country. Another key strength is research into the genetic and lifestyle factors that increase the risk of cancer, building on decades of experience in this area. Oxford scientists first showed that smoking causes cancer more than 40 years ago, and researchers in the city have made many more major discoveries in understanding the causes of the disease. Other areas of expertise at the Oxford centre include research into the faulty genes and molecules that lie at the heart of cancer. Researchers will also be investigating ways to improve cancer diagnosis, as well as searching for 'biomarkers' to help doctors predict the effectiveness of cancer treatment. A major aim of the Oxford centre is to bring benefits to cancer patients faster than ever before. To achieve this, the University has established a new Department of Oncology next door to the new Oxford Cancer Centre at the Churchill hospital in the city. This will help to build stronger links between researchers working in the lab and doctors caring for cancer patients, speeding up the creation of new treatments. Finally, the centre is designed to be part of the community in and around Oxford. Working with our Local Engagement and Development team, researchers will engage with local people to raise awareness of cancer and the world-class research on their doorstep.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Competitive cell interactions in normal physiology and cancer
Funder: Cancer Research UK

Abstract: BACKGROUND: An important goal of modern Biology is to understand how cells communicate across tissues to coordinate proliferation, differentiation and survival. Our research focuses on one type of cell communication called cell competition, whereby cells in tissues compete for survival and less fit (‘loser’) cells are induced to die. Work in drosophila has shown that cell competition can be triggered by cellular differences in ribosomal production, c-Myc activity, TGFbetaDpp signaling and Fat/Hippo signalling. Moreover my recent work also in drosophila shows that cells with high Wnt (Wingless) signalling levels induce apoptosis in neighbouring wild-type cells via cell competition. RELEVANCE TO CANCER: Because most known competition factors have been implicated in cancer, it is thought that cell competition is co-opted by ‘super-fit’ cancer cells to kill surrounding normal cells and boost tissue colonization. Interestingly, suppressing cell death in the ‘loser’ cell population is sufficient to inhibit the overgrowth of ‘winner’ cells. Thus, inhibiting cell competition could impair cancer growth. SPECIFIC AIMS OF THE RESEARCH: The research described in this proposal has the following objectives: - Elucidate the molecular mechanisms of Wnt-signalling induced competition. - Identify novel triggers and regulators of cell competition. - Elucidate the role of competition in adult tissues and in the regulation of cellular turnover during adult tissue homeostasis. - Elucidate the importance of cell competition in a drosophila model of intestinal adenoma. - Investigate cell competition in mammalian cells and elucidate the involvement of specific oncogenes in cell competition. OUTLINE PLAN OF RESEARCH: To achieve these objectives we will combine work in drosophila larvae with approaches using adult drosophila tissues and mammalian cells in culture. Specifically: - We will continue our work using drosophila wing discs and combine it with next generation sequencing to identify genes involved in Wnt-induced competition. - Using drosophila wing discs we will also perform a RNAi screen to identify novel regulators of cell competition. - We will study how competition regulates adult tissue homeostasis, by setting up a system to induce cell competition in the adult drosophila gut. - We will also use this system to specifically address the importance of cell competition in the context of drosophila Wnt-induced intestinal tumours. - Finally, we will establish cell-based assays to study competition among mammalian cultured cells. We will then film competing cells to study the spatiotemporal dynamics of competition and use next generation sequencing to identify genes involved in mammalian cell competition.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/06/009: LungStar - A multicentre phase III randomised double blind placebo controlled trial of pravastatin added to first-line standard chemotherapy in patients with small cell lung cancer (SCLC)
Funder: Cancer Research UK

Abstract: Background and relevance to cancer_x000D_ Despite benefit with chemotherapy for small cell lung cancer (SCLC), overall survival remains poor. Consequently, new therapies are urgently required, which can be added to existing treatments to increase survival without unacceptable toxicity. Statins exert potent antiproliferative / pro-apoptotic effects in SCLC in vitro and in vivo and are also additive with chemotherapy. Moreover, they are active against many other tumour types. However, statins have not yet been tested in a large randomized trial for their beneficial effect against any cancer type._x000D_ Aims and objectives._x000D_ Here, we will primarily determine whether pravastatin when added to standard chemotherapy in SCLC improves overall survival. Other endpoints include response rates, progression free survival, and toxicity._x000D_ Methods_x000D_ This is a multicentre, double blind, randomized placebo controlled phase III trial of pravastatin added to standard chemotherapy with cisplatin or carboplatin and etoposide. Oral pravastatin or placebo will be given from the start of chemotherapy for a maximum of 2 years_x000D_ Parallel blood and tissue collection will enable gene, protein and metabolic profiling techniques to identify predictive markers of survival and response to study treatment_x000D_ How the results will be used_x000D_ Our results will be published and used to determine standard of care for patients with SCLC


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Belfast Cancer Research UK Centre (Clinical Training Account)
Funder: Cancer Research UK

Abstract: Clinical training associated with a centre: As one of the first centres, the Belfast Cancer Research UK Cancer Centre will help set the pace for national and international progress in cancers of the bowel, oesophagus and breast. It will also concentrate on pioneering the latest techniques in radiotherapy, improving cancer diagnosis and developing new, more effective drugs. The Centre aims to be a world leader in developing treatments tailored to individual cancer patients based on understanding the biology of the disease and how that varies among patients. Collaborations - a cornerstone of this virtual Centre - will focus on identifying new targets for cancer drugs, understanding how genes can help predict which treatment will be most effective, and developing specific new treatments that have fewer side effects. The Centre is a partnership between Queen's University Belfast, the Northern Ireland Health and Social Services Central Services Agency's Research and Development Office, Belfast Health and Social Care Trust and Cancer Research UK.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Development of selective CDK9-cyclin T1 pharmacological inhibitors for the treatment of chronic lymphocytic leukaemia
Funder: Cancer Research UK

Abstract: (1) Background CLL is the most common type of leukaemia and accounts for half of all leukaemias in older adults. CLL cells are characterised by resistance to apoptosis mediated by the over-expression of anti-apoptotic proteins. Several clinical CDK inhibitors including flavopiridol have demonstrated excellent anti-CLL efficacy by targeting CDK9-cyclinT1. However these compounds also target other CDKs that may result in toxicity because of anti-proliferative effects on normal cells. (2) Relevance to Cancer Resistance to apoptosis is feature of CLL and many other tumours including AML, ALL, MM, melanoma, prostate, pancreatic, breast and ovarian cancers. Therefore the development of specific CDK9 inhibitors represents a rational therapeutic strategy. (3) Specific aims We have successfully identified a novel class of CDK9 inhibitors that selectively induced apoptosis in patient-derived CLL cells. This project aims to: (1) optimise the current lead series for CDK9-selectivity and specificity; (2) identify a back-up compound series distinct from the lead series in order to maximize the chance of success in generating mono-specific CDK9 inhibitors; (3) identify preclinical lead compounds as potential therapeutics. (4) Outline plan of research We have excellent design-strategies in place for generating CDK9 inhibitors with optimal specificity. The compounds will be assessed using our established testing cascade. Promising compounds will be further assessed for ADME/PK properties (see full research proposal).


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Role of a novel RNA methyltransferase in miRNA function and cell proliferation
Funder: Cancer Research UK

Abstract: BACKGROUND: In the course of screening for new histone methyltransferases, we identified a novel enzymatic activity capable of methylating the 5'-alpha phosphate of RNAs. A specific iRNA has been identified as a target for this methylation activity. The novel methyltransferase and its miRNA target have been linked to cancer, consistent with our finding that this enzyme is a regulator of cell proliferation. RELEVANCE TO CANCER: We have established that the siRNA-mediated depletion of this RNA methyltransferase leads to a severe proliferation defect in human cancer cell lines. These preliminary results are in accordance with observations that its mRNA is over-expressed in highly tumorigenic breast cancer stem cells. In addition, the RNA methyltransferase is present in a gene list associated with an "invasiveness" gene signature linked to poor prognosis. Taken together, these data suggest that this enzyme may act as an oncogene and that it may represent a novel class of enzyme target for pharmacological intervention. SPECIFIC AIMS: Our main objective is to establish how methylation of RNAs by this methyltransferase regulates their function and potentially leads to cancer. To do this we will: - Identify the set of RNAs targeted by the methyltransferase. - Define the mechanisms by which RNA methylation regulates RNA activity and how this enzyme is regulated by protein partners. - Establish the role of this methyltransferase, its partners and its RNA targets in cell proliferation. OUTLINE PLAN OF RESEARCH: We will first isolate novel RNA targets for methylation by assessing the 5’ methylation status of RNAs that co-immunoprecipitate with the RNA methyltransferase and by analysing a panel of known miRNAs. Target RNAs will then be examined for the effect of methylation on their stability. Proteins will be isolated that bind preferentially to the methylated version of the target RNAs by RNA-pull down coupled with SILAC and Mass Spectrometry to provide a mechanism of action. Proteins bound to this new RNA methyltransferase will be identified by immunoprecipitation coupled with SILAC and Mass Spectrometry, in order to define the pathways regulated by this enzyme. Finally, the RNA methyltransferase, its protein partners and target RNAs will be evaluated for their ability to control proliferation of breast cancer cell lines and induce tumours in mammary fat pads.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Colorectal cancer and Wnt signalling
Funder: Cancer Research UK

Abstract: Colorectal Cancer is the third most common cancer in the western world. The focus of the colorectal cancer and Wnt signalling group is to try to understand the early changes associated with intestinal neoplasia to identify novel markers of disease and new targets for therapy. The key intestinal tumour suppressor is the Apc gene which is mutated in approximately 80% of sporadic cancer. Germline heterozygosity of Apc leads to Familial Adenomatous Polyposis. Central to our work is the use of novel inducible models of intestinal tumourigenesis which allow us to study the functions of specific tumour suppressor genes.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Stem cell & haematopoiesis
Funder: Cancer Research UK

Abstract: Overview The haematopoietic and endothelial lineages derive from mesoderm and are thought to develop through the maturation of a common progenitor, the hemangioblast. The major focus of our studies is to understand the relationship between mesodermal precursors and the hemangioblast, and to define the molecular and cellular mechanisms that regulate lineage commitment of this earliest known blood precursor. To study these questions, we use the in vitro differentiation potential of embryonic stem cells as a model system. We have developed embryonic stem cells with the green fluorescence protein targeted into the brachyury locus, a marker of the mesoderm germ layer. Using this tool, we can follow and analyze mesoderm subpopulations and hematopoietic precursors.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CANCER AND NEOPLASMS
Title: Stem cell biology
Funder: Cancer Research UK

Abstract: Overview The AML1/Runx1 transcription factor and its cofactor CBFb, are frequent targets of gene rearrangements and mutations in human leukemias such as acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL). Consistent with its initial implication in leukemias, Runx1 has been shown to be critical for normal hematopoietic development. Runx1 deficient murine systems generate primitive nucleated erythrocytes, but lack all definitive erythroid and myeloid cells, indicating a complete block in definitive hematopoiesis. Using the in vitro differentiation system based on murine embryonic stem (ES) cells, our goals are to further define the role of Runx1 in early hematopoietic development and how alterations of its function leads to leukemogenesis.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Chemistry Laboratory
Funder: Cancer Research UK

Abstract: My research applies the principles of chemistry to provide new insights into molecular mechanisms that are of importance to the biology of cancer. My group's major research area explores new ways to control cancer-causing genes that are often found to be over-active in various cancers. We have developed methods to synthesise small drug-like molecules that have the potential to 'switch-off' cancer causing genes and by so doing, inhibit the growth of cancer cells. The drug molecules have the potential to work in a way that avoids general toxicity towards cells and may also avoid some of the drug resistance problems observed from approved cancer drugs.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Birmingham Cancer Research UK Centre (Clinical Training Account)
Funder: Cancer Research UK

Abstract: Clinical Training associated with the Centre: As the first Cancer Research UK Centre, Birmingham will set the pace for national and international progress for genetics, gene therapy and the link between viruses and some cancers as well as focussing on cancers of the prostate and bladder and leukaemia. It will also become a leading centre for clinical trials. The Centre - a virtual framework - is a partnership between the University Hospitals Birmingham NHS Foundation Trust, the University of Birmingham and Cancer Research UK. Collaboration is the key to the success of the Centre which will also concentrate on large-scale population studies, cell biology and tumour immunology. The research community here already receive funding from Cancer Research UK but the Centre's initiative will increase the charity's contribution to supporting research in Birmingham to around ú9m a year. Cancer Research UK Centres aim to establish a nationwide network of excellence that will provide the best possible outcomes for patients by linking research activity with patient care and public engagement. Each Centre will focus on specific areas of research and aim to raise standards of care and forge links with local communities. The Centres's programme will enable Cancer Research UK to implement its research strategy and achieve its vision and purpose.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Southampton Cancer Research UK Centre (Non-Clinical Training Account)
Funder: Cancer Research UK

Abstract: The Southampton Cancer Research UK Centre is a network bringing together scientists, doctors and nurses in the area. They are using the latest research advances to improve treatment for cancer patients in and around Southampton and across the UK._x000D_ _x000D_ The Centre is a partnership between Cancer Research UK, the University of Southampton, and Southampton University Hospitals NHS Trust._x000D_ _x000D_ Researchers in the Centre are focusing on breast cancer and urological cancers - principally testicular, bladder and kidney cancers - as well as lymphoma. But they are also working on many other types of cancer, including tumours affecting the head and neck cancer, and liver and bile duct cancers._x000D_ _x000D_ The Southampton Cancer Research UK Centre is a world-class centre of excellence for research into immunotherapy – how to harness the power of the immune system to treat cancer. The first DNA cancer vaccines were developed here, and scientists at the Centre are at the cutting edge of this exciting field._x000D_ _x000D_ Another area of strength in the Centre is cancer genetics – hunting the gene faults that increase an individual’s risk of cancer. And there is also an emphasis on cancer surgery - particularly for head and neck cancers and breast cancer - including focusing on research into this vital treatment._x000D_ _x000D_ Southampton has a strong track record in training outstanding cancer scientists, doctors and surgeons – a tradition that is set to continue and grow. The Centre provides the right environment for training the next generation of experts, to ensure that we continue to make progress in beating cancer._x000D_


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Newcastle Cancer Centre at the Northern Institute for Cancer Research (Clinical Training Account)
Funder: Cancer Research UK

Abstract: Clinical training associated with: Newcastle has now joined the charity's unique network of 'virtual' centres delivering world-class science and improved patient care. The new Centre puts Newcastle at the forefront of cancer research and will bring benefits to patients in the North East.<br/><br/>The Centre is not a new building, but instead is a collaboration between Cancer Research UK, the Leukaemia Research Fund and the North of England Children's Cancer Research Fund. This will make it easier for scientists to work together with doctors and nurses, so patients can benefit from research breakthroughs more quickly.<br/><br/>Research at the Centre will concentrate on understanding the basic biology of how and why cancers develop, with a particular focus on blood cancers, such as leukaemia, and childhood cancers.<br/><br/>Scientists in Newcastle have an impressive track record in the discovery and development of new anti-cancer drugs. Researchers at the new Centre will focus on developing treatments that can be tailored to the genetic 'signature' of an individual cancer patient, instead of a one-size-fits-all approach. This will help to avoid unnecessary side effects and improve survival rates.<br/><br/>Clinical trials are an important aspect of the Newcastle Centre for Cancer Research. Through this initiative, we aim for more cancer patients in the North East to be given the opportunity to take part in trials of the latest treatments. Grants support a variety of training projects - where available coding is done on the basis of these individual pieces of research.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Molecular Biology of Urothelial Cancer
Funder: Cancer Research UK

Abstract: Bladder tumours comprise at least two major groups with distinct clinical phenotypes and molecular characteristics. Within these groups, patient outcome varies widely and there is a pressing need for improved understanding of their molecular pathogenesis and classification of clinically relevant subgroups. Our aim is to identify molecular alterations that define such subgroups. Copy number and mutation analysis of tumours from both major groups (all grades and stages) with long-term clinical follow-up information will be followed by more extensive genome-wide examination of samples representing potential subgroups. Functional validation of selected genes that may define subgroups will be carried out in cultured normal and tumour-derived human urothelial cells. This information will be applied in the clinical setting to improve tumour classification at diagnosis and potential biomarkers will be tested for predictive and prognostic value.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS