NIHRDataInsights/HRCSData huggingface dataset:
Title: Cancer Research UK Centre for Cancer Therapeutics - Cell cycle control team
Funder: Cancer Research UK

Abstract: One of the principal characteristics of human cancer is the ability to proliferate in an uncontrolled manner. At the heart of cell proliferation is the cell division cycle and, when not regulated correctly, this process can be one of the underlying causes of cancer. The main aims of the Cell Cycle Control Team are (i) to further our understanding of how signalling pathways regulate the mammalian cell division cycle through the cyclin dependent kinase (CDK) family of serine/threnonine kinases and to use this knowledge to identify and validate cell cycle regulators as targets for therapeutic intervention in cancer (ii) to participate in drug discovery and development projects that can utilise our expertise in signalling pathways and cell cycle regulation. In particular, we are interested in the cyclin D-dependent kinases CDK4 and CDK6, which associate with the D-type cyclins to control G1 progression through phosphorylation of the tumour suppressor protein, pRb. Most human cancers contain genetic alterations that affect these kinases, their regulators including the D-type cyclins or pRB itself. In addition they act as a key integration point between extracellular signalling pathways such as those governed by Ras and PI3 kinase/protein kinase B and the cell division cycle. Thus, understanding the molecular basis of the CDK/cyclin D/pRb pathway and its regulation will be important in the identification of novel targets for new cancer treatments. We are also participating in four drug discovery and development projects. These are on PKB, pRb phosphorylation and the Chk1 and Chk2 cell cycle checkpoint kinases


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Mechanism of Gene Transcription Laboratory
Funder: Cancer Research UK

Abstract: PREVIOUS AND CURRENT RESEARCH: During transcript elongation, RNA polymerase II (RNAPII) faces two major obstacles to its progression: chromatin structure and DNA damage. The ability of cells to deal with these challenges is essential for efficient transcription, disease prevention, and survival. To elucidate basic mechanisms of transcriptional elongation, we have isolated the elongating form of RNAPII and found that it is a holoenzyme, consisting of core polymerase and a complex, called Elongator. One of the subunits of Elongator, Elp3, is a histone acetyltransferase, suggesting that the Elongator complex helps RNAPII to transcribe through chromatin. We are presently undertaking a thorough characterisation of the Elongator complex by a combination of biochemical and genetic approaches in both yeast and human cells. We have also isolated the 'transcription-coupling repair factor', Rad26 (yeast Cockayne's Syndrome B protein). Rad26 is associated with a novel factor, termed Def1. Our present work on the function of the Rad26-Def1 complex is shedding new light on the mechanism of transcription-coupled repair in eukaryotes. FUTURE PROJECTS: With our isolation of Elongator and the Rad26-Def1 complex, we are one step closer to an important immediate goal of our research: reconstitution of transcription-coupled repair, as well as transcription-coupled chromatin remodelling in vitro. We expect that such reconstitution will lead to the identification of a number of new protein factors. Using yeast as a model system, and with immediate use of human cells to verify and extend the initial observations done in the model organism, we aim to achieve a thorough understanding of transcript elongation in eukaryotic cells in general. In the longer term, our aim is thus to understand the cellular mechanisms that couple transcript elongation to genome integrity. We believe that this research will prove important for understanding basic biological processes that lead to human diseases such as cancer.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CANCER AND NEOPLASMS
Title: CRUK/10/018: ART-DECO: A randomised accelerated radiotherapy study of dose escalated IMRT vs conventional dose IMRT in patients receiving treatment for Laryngeal and Hypopharyngeal cancer.
Funder: Cancer Research UK

Abstract: A randomised multicentre accelerated radiotherapy study of dose escalated IMRT (67.2 Gy) vs Standard dose IMRT (65 Gy) in patients receiving treatment for locally advanced laryngeal and hypopharangeal cancers. (ISRCTN: 1483375).http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=9562


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Genetic Recombination Laboratory
Funder: Cancer Research UK

Abstract: Our genetic material (DNA) is continually subjected to damage, either from endogenous sources such as reactive oxygen species produced as by-products of oxidative metabolism, from the breakdown of replication forks during cell growth, or by agents in the environment such as ionising radiation or carcinogenic chemicals. To cope with such damage, cells employ a variety of repair processes that are specialised to recognise different types of lesions in DNA. These repair systems are essential for the maintenance of genome integrity and for cancer avoidance. The focus of our research is to determine the cellular mechanisms for repair and, most importantly, to define the cellular defects that lead to cancers and neurodegeneration, two common consequences of defective damage processing. Our present work focuses on the molecular analysis of proteins such as BRCA2, GEN1, MUS81-EME1, SLX1-SLX4, FANCM and SEN1.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Liverpool Cancer Research UK Centre (Core)
Funder: Cancer Research UK

Abstract: The Liverpool Cancer Research UK Centre - the second centre to launch in our Centres programme - will set the pace for national and international progress in pancreatic, head and neck, and blood cancers. It will also concentrate on pioneering the latest techniques in surgery, radiotherapy and the treatment of children's cancers. Collaboration is the key to the success of this virtual Centre, a partnership between the Royal Liverpool University Hospital, Clatterbridge Centre of Oncology NHS Trust, the University of Liverpool, the Liverpool City Council, the Merseyside and Cheshire Cancer Task Force, and Cancer Research UK. It 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. Researchers will also be focusing on a better understanding of how cancers start and behave, developing more effective treatments with fewer side effects, and tackling cancer in low-income communities where survival is lowest.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Identification of regulators of metastasis in uveal melanoma (UM).
Funder: Cancer Research UK

Abstract: Uveal Melanoma (UM) is the most common primary intraocular cancer in adults. It is fatal in approximately 50% of patients, almost always because of metastatic spread to the liver. Chemotherapy rarely prolongs life and long-term survival is rare unless the hepatic metastases are resectable. Metastatic disease occurs almost exclusively in patients with monosomy 3 melanoma. However, fatal disomy 3 UM do occur occasionally. This unexpected outcome can be explained by: (a) poor resolution of routine cytogenetic techniques (e.g. fluorescence in situ hybridization, FISH) and (b) additional genomic changes being involved in UM metastasis. Indeed, our group has demonstrated a strong inverse correlation between polysomy 8q and survival in UM. Preliminary investigation of 3 fatal UM using the Affymetrix SNP 6.0 array (aSNP) detected 102 microdeletions on chromosome 3. This suggests that genes particularly important in preventing metastasis are lost in these UM. It is also possible that the observed microdeletions represent homozygous changes following duplication of an aberrant copy of chromosome 3 (i.e., uniparental disomy). This genetic change has previously been reported in UM at a frequency of 6%. We hypothesise that: • Mutation or deletion of genes on the remaining copy of chromosome 3 in monosomy 3 UM (Mo3Met) contributes to the increased metastatic potential of these tumours. • Metastatic UM with apparent disomy 3 (Di3Met) is associated with duplication of an aberrant copy of chromosome 3 (uniparental disomy). • Amplification or mutation of genes on chromosome 8q contribute to metastatic potential. To test these hypotheses we will: • Compare genomic aberration profiles in primary UM with and without metastasis using aSNP and massively parallel sequencing. • Identify and validate candidate genes involved in the metastatic process in a large cohort of primary UM with known histomorphological characteristics and survival data by immunohistochemistry or quantitative RT-PCR. • Use UM cell lines to understand the functional significance of genetic changes associated with UM metastasis. The effects of over-expression, knock-down or mutation of candidate genes on proliferation, motility and invasion will be tested by standard procedures (e.g. wound-healing assays to assess cell motility, and cell invasion assays through a basement membrane such as Matrigel). Ultimately, identification of the key loci responsible for metastatic UM and a better understanding of their functional role should improve prognostic testing, and may identify key pathways for targeting individualized therapies.


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

Abstract: Current strategies in the development of new therapies for malignant disease are based on exploiting our increasing understanding of the molecular basis of cancer. Work in our group is aimed at developing novel laboratory models that allow us to determine how potential anti-invasive agents might best be evaluated in subsequent clinical trials, and by developing biomarkers of antitumour activity to specific agents that can be applied to biological samples in clinical trials. The classical paradigm for developing cancer therapeutics is dependent on demonstrating a reduction in tumour size on serial clinical or radiological assessments as an indication of anti-tumour activity. However tumour volume is a complex integral of growth, involution, necrosis and inflammatory processes, and so alone it is not the most appropriate parameter in determining response. Coupled with this, the current generation of molecular-targeted therapies have been designed to inhibit specific molecular processes and may not consistently result in objective tumour reduction in patients with advanced refractory tumours despite producing their desired biological effect. We are focusing on overcoming this problem.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Cardiff Cancer Research UK Centre (Core)
Funder: Cancer Research UK

Abstract: The launch of the Cardiff Cancer Research UK Centre will help set the pace for progress in genetics and cancer biomarkers. Part of Cancer Research UK's national network of virtual cancer research centres, the Cardiff 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 it varies among patients. Researchers at the Centre will focus on the biology and treatment of bowel, breast and urological cancers as well as leukaemia. Working with the Wales Office of Research and Development for Health and Social Care (WORD), they will also work on better understanding how to prevent cancer and detect the disease earlier. Cancer Research UK is looking to increase its contribution to research in Cardiff by spending an extra £2 million over three years - this boost will enable Cardiff to continue leading the way on cancer research in Wales. The Centre will also continue Cardiff's excellent record of training the next generation of clinical and non-clinical researchers - aiming to expand the existing four-year PhD programme together with Cardiff University. The Cardiff Centre is a partnership between Velindre NHS Trust, Cardiff and Vale NHS Trust, Cardiff University and Cancer Research UK.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);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: Cancer Epidemiology Unit
Funder: Cancer Research UK

Abstract: 1) Background to the proposal Over the last decade we have established some of the largest epidemiological studies in the world on the avoidable causes of cancer. The uniqueness and relevance of our work is illustrated by the large number of citations to our publications – over 10,000 since our last CR-UK review. Long-term stable funding has enabled the development and maintenance of these exceptional studies. 2) Relevance to cancer Results from our ongoing prospective studies and major national and international collaborations will yield uniquely reliable evidence on ways of reducing cancer risk. 3) Specific aims of the research Specific aims in the next 4 years include to: - bring together and re-analyse the worldwide epidemiological evidence on 130,000 women with breast cancer, to assess the effects of different types of hormone replacement therapy and of oral contraceptive use that began in adolescence; - design and monitor a randomized trial of one million UK women on the benefits and harms of an additional screen within the NHS Breast Screening Programme; - investigate further the role of diet, and of markers of dietary intakes in the blood, in prostate cancer, including the bringing together of relevant worldwide evidence; - study how diet and other factors affect blood levels of growth factors, and how they affect cancer risk; - use our low-cost web-based automated questionnaires to augment dietary and other data in our prospective studies; - conduct large-scale studies of the potentially avoidable causes of ovarian, endometrial, colorectal and oesophageal cancer. Our current studies will continue to yield important results for at least another decade, and the work proposed for the next 4 years is only part of what can be achieved in the long term. 4) Outline plan of research Most of the work will use data from the continued follow-up and appropriate enhancements of our large ongoing prospective studies, the Million Women Study and EPIC-Oxford, our collaboration with the NHS Cancer Screening Programmes, and the worldwide collaborations we lead on breast, prostate, ovarian and endometrial cancer. We will hold regular meetings with collaborators to discuss methodological issues and preliminary results. Our findings will be published in peer-reviewed scientific journals and, when they have important public health implications, will be disseminated more widely.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.4 SURVEILLANCE AND DISTRIBUTION;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Cancer survival
Funder: Cancer Research UK

Abstract: We will monitor cancer survival trends and inequalities. We will examine the influence of diagnostic delay, treatment and co-morbidity on inequalities in survival between socio-economic and ethnic groups. We will develop new research methods, contribute to government policy, support CRUKÆs strategic goals, and keep cancer patients and the public informed. Background Our research focusses on (a) trends and inequalities in cancer survival and their population impact; (b) the causes of inequalities in survival, and (c) the impact of strategies designed to improve survival and reduce inequalities. Relevance Cancer survival in the UK is rising, but socio-economic inequalities for many cancers are still widening. Ethnic differences in survival can now be examined. The impact of co-morbidity and treatment can also be examined by linking individual tumour records in the national cancer data to primary care records and hospital episode data. This research programme is designed to advance knowledge on the causes of and possible solutions for inequalities in survival. Aims and outline of research programme We will examine: - the impact of clinical and healthcare system factors (diagnostic investigation, stage, treatment, co-morbidity and its timing in relation to the cancer diagnosis) on inequalities in population-based cancer survival - how the indices used to measure socio-economic status affect inequalities in survival - ethnic variation in survival, and whether socio-economic inequalities in survival affect all ethnicities We will extend our research on the formulation of health policy for cancer control, by examining: - the impact of the NHS Cancer Plan (England) on survival trends and inequalities, and assessment of the impact of treatment guidelines - the impact of the definition of Spearhead Primary Care Trusts on geographic inequalities in survival - trends in avoidable excess cancer mortality relative (a) to cancer survival in Europe and (b) to socio-economic inequalities in survival within the UK We are investigating or developing methods: - to derive robust, complete life tables from sparse data on deaths and populations - to quantify avoidable deaths that can be attributed to inequalities in relative survival - to quantify the proportion of variation in survival that can be explained by co-variables - to provide additional functionality for our survival analysis software (strel) - to simulate differential under-registration by socio-economic status and duration of survival - to explore regional and temporal variations in survival using funnel plots - to produce more robust indices of survival for cancer con Last updated 21/07/2010


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES);8.2 HEALTH AND WELFARE ECONOMICS
Health categories: CANCER AND NEOPLASMS
Title: Do hormonal treatments for assisted reproduction in women increase risks of cancer or mortality? A national cohort study.
Funder: Cancer Research UK

Abstract: The use of fertility drugs is increasing in the UK. Some studies have indicated raised risks of certain cancers in such patients, but this remains uncertain. We will study these risks and mortality risks in a cohort study of all assisted reproduction patients nationally for the last 15 years. Last updated / / Brief background: Assisted reproductive techniques (ART), and in particular IVF, are now regarded as an NHS priority with falling fertility rates, rising mean patientÆs age at first child birth and other socialtrends. Fertility drugs usage is increasing and even if superovulation increases the chances ofconceiving, attention has been focused on the possible association between the use of these drugsand the long term risk of development of malignancies of the ovary, breast, endometrium and other cancers.Relevance to Cancer: 200,000 women have had fertility treatments in the UK since 1991 (HumanFertilisation and Embryology Authority (HFEA) registry figures).If these hormone treatments or someother aspect of ART increase the risk of cancer, then careful counselling and follow-up will be needed for patients experiencing sub fertility .Consideration as to which types of treatments are safest (e.g. natural cycle IVF) will be needed to reduce risk.The aims of this project will be:1. To investigate the relationship between ART treatment and site-specific risks ofcancer incidence, especially reproductive-related cancers, in relation to type of treatment, especially type, duration, and age of exogenous hormone exposure.2. To establish if there is any link between cause-specific mortality risks and ART exposure..Study design: longitudinal retrospective population cohort studyMethods: Due to a change in the HFEA act (valid from October 2009) it is now possible for the firsttime to (with due caveats) access personal data from the HFEA registry. The registry isinternationally unique and contains detailed information on 600,000 cycles of ART in 200,000women. That would be potentially 4 x size of the largest published study and the first to investigate all cause mortality after ART. Identifiers of cohort members will be linked to the NHS Central Registries, with æflaggingÆ to enable identification of cancer incidence, mortality, and other follow-up in the cohort. Observed ôsite-specific cancer incidence rates and cause-specific mortality in the cohort will be compared with expectations derived from national cancer and mortality rates, to calculate relative risks of cancer and mortality in relation to type, age and duration of hormonal treatment. The flagging will also provide a resource for future similar analyses with longer follow-up. Last updated / /


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS
Title: Long term health outcomes after treatment for cancer in teenage and young adulthood
Funder: Cancer Research UK

Abstract: Identify subgroups of the almost 300,000 individuals diagnosed with cancer aged 15 to 39 years, in England and Wales, between 1971 and 2006 at substantially increased risk of particular fatal or non-fatal adverse health outcomes.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS