NIHRDataInsights/HRCSData huggingface dataset:
Title: CRUKE/11/059: TRIOC trial- A randomised parallel group double-blind phase II study to assess the activity of TroVax® (MVA-5T4) versus placebo in patients with relapsed asymptomatic epithelial ovarian, fallopian tube or primary peritoneal cancer- tumour sample collection
Funder: Cancer Research UK

Abstract: TRIOC study is a randomised parallel group double-blind phase II study to assess the activity of TroVax® (MVA-5T4) versus placebo in patients with relapsed asymptomatic epithelial ovarian, fallopian tube or primary peritoneal cancer. TroVax® is a cancer vaccine composed of a highly attenuated recombinant vaccinia virus that contains a gene encoding the human 5T4 oncofetal antigen. This gene has been found to be highly upregulated in ovarian cancer and many other cancers. Ovarian cancer is a common cancer that has a poor outlook despite improvements in treatment and diagnosis. There is extensive evidence that ovarian cancer is under immune surveillance. A study reported by Zhang et al in 2003 showed that 5-year overall survival correlates with the presence or absence of tumour infiltrating lymphocytes (TILs) in favour of patients who show immune response (38% versus 4.5%, respectively, p0.001) [1]. Similarly patients with higher CD8 expressing TILs showed improved survival [2]. 5T4 is highly expressed in ovarian cancer [8]. The expression of 5T4 correlates with more advanced stage of disease (FIGO stages III and IV) (P0.001) and with poorly differentiated tumours (P=0.036). Patients whose tumours express 5T4 appear to have a worse outlook in terms of survival and disease-free interval (P=0.033) [8]. There is extensive pre-clinical and some clinical experience with TroVax. Studies in prostate, renal and colorectal cancer proved that TroVax is able to elicit immune response, both cellular and humoral responses in patients with cancer. In some of the studies the magnitude of immunological, cellular and humoral response reached 90%. The clinical responses were reported however at a much lower rate. The aim of the current study is to look at the effect of TroVax in women with low volume relapsed disease and to assess response both clinical: using RECIST and Immune-related Response Criteria as well as immunological response by measuring 5T4 specific antibodies and cytotoxic T cells. We plan to collect tissue samples to look at the expression of 5T4 in tissue but also to look at the immunological aspects of tumours and patients who respond to treatment as compared to those who do not respond. All patients who will participate in the trial will be asked for permission to use archival tissue. The tissue will be collected from all centres participating in the trial and the collection is mandatory for all patients. The analysis will take place once the trial has closed and all patients complete treatment.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Gene expression patterns as a readout of polygenic susceptibility; potential applications to risk estimation and to prevention in lung cancer
Funder: Cancer Research UK

Abstract: Understanding Lung Cancer Risk Aims: To harness the power of genetic research to help people with a high risk of lung cancer. Lung cancer is the biggest cancer killer in the UK, taking around 96 lives every day. By the time the disease is diagnosed, it has often already spread, making it very hard to treat. Although most cases of the disease are caused by smoking, inherited genetic changes also play a part in determining each person’s risk of the disease. This programme will attempt to change the odds for people with lung cancer by finding a way to identify those who are most at risk. The group will collect tissue and lung cancer samples from smokers and ex-smokers (patients and people who don’t have cancer). The aim is to identify key genetic changes that can help researchers understand each person’s risk of developing the disease. They hope that this ambitious project could help spot smokers and ex-smokers with the highest risk of lung cancer. In the future it could be possible to offer these people tailored screening to ensure the disease is diagnosed as early as possible.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Centrosome Biology Laboratory
Funder: Cancer Research UK

Abstract: We have three major goals in the laboratory. First, we want to understand how the vertebrate centrosome assembles and functions. Second, we want to address what consequences deregulation of centrosomal proteins hold to mitotic spindle formation and genomic stability. Third, we want to study the molecular mechanisms and signals that govern centrosome behaviour and positioning in response to environmental cues. These goals aim to provide insight into basic biological processes whose deregulation is implicatedin the development of cancer.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Stem Cell Biology of the Intestine
Funder: Cancer Research UK

Abstract: The greatest number of cancers occur in the epithelial linings of major organs such as the intestine which are maintained by small numbers of long lived stem cells. It is by disruption of the normal molecular controls regulating stem cell growth, behaviour and programming that cancers develop. The group seeks to understand the normal biology of epithelial stem cells, and how this is subverted to allow cancers to form. A particular goal is to develop clonal approaches in which gene specific mutations are switched on as rare sporadic events. In so doing we are replicating the aetiology of cancer to investigate the relationship between stem cells and epithelial cancers. Research topics include: Develop and apply strategies to induce specific gene mutations within epithelal tissues in a transgenic setting. Develop a mitotic clock to determine the frequency of stem cell division. To determine the composition and heterogeneity of stem cells in terms of their commitment to different cell lineages and proliferative potential. To determine the molecular pathways controlling stem cell fate and behaviour. To understand to what extent the stem cell characteristics of normal tissues are retained in epithelial cancers and if these can be exploited to develop therapeutic interventions. To understand at a cellular level how cancer predisposing mutations lead to the growth of neoplastic lesions. To test the efficacy of different therapeutic and preventative interventions applied at a defined stage of cancer growth."


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Cross-centre Molecular Pathology Training- the NewBel collaboration
Funder: Cancer Research UK

Abstract: Access to well characterised human tissues underpins many aspects of contemporary cancer research and is central to the translational research strategies of the ECMCs based in Newcastle and Belfast. The proposed placement will strengthen the links between our centres by the sharing of expertise in tissue processing and molecular diagnostics. The longer term aim is to accelerate tissue-based research projects by pooling access to well-established tissue banks already in place at both centres- the Northern Ireland Biobank and the Newcastle Cancer Centre Biobank with the formation of the “NewBel” collaboration. Dr Jennifer Jackson has been nominated to spend to spend 6 months working in the molecular diagnostics laboratory in the molecular diagnostics laboratory, Queen’s University, Belfast, Headed by Professor Manuel Salto-Tellez. Professor Salto-Tellez is an internationally recognised expert in the field of tissue-based molecular diagnostics and the recently reconfigured laboratory in Belfast offers an ideal training opportunity for Dr Jackson- who is currently employed as the histopathology lead in the Newcastle Cancer Centre. During her placement in Belfast Dr Jackson will gain expertise in 1) General pathology (tissue processing, embedding, banking, H&E preparation, manual and automated immunohistochemistry and in situ hybridisation), 2) Digital microscopy techniques, 3) TMA preparation and analysis 4) RNA and DNA extraction for molecular pathology (FFPE) and 5) General tissue histology interpretation. As well as providing a service for other members of the Newcastle ECMC Dr Jackson will offer training to research associates and technicians to broaden the skill base within the Centre. The proposed cross-centre placement forms part of a larger initiative to enhance collaboration between the ECMCs and Cancer Centres in Belfast and Newcastle. By pooling our expertise, particularly in biobanking and early clinical trials, we shall be able to increase our rates of patient accrual for translational and clinical research.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: LungSearch Follow up - A randomised controlled trial of surveillance for the early detection of lung cancer in an at risk group
Funder: Cancer Research UK

Abstract: Background: The majority of lung cancers are diagnosed at advanced stages when curative treatment is not possible. Recent developments in sputum cytology, computed tomography (CT) and auto-fluorescence bronchoscopy (auto-FB), however, raise the prospects of detecting early stage lung cancers and pre-neoplastic lesions. Relevance to cancer: If sensitive diagnostic techniques are used to evaluate high-risk patients, it may be possible to detect lung cancers at earlier stages when curative treatment is feasible, while the identification of pre-neoplastic lesions may enable some lung cancers to be prevented, thereby improving survival prospects. Specific research aims are to: • determine whether yearly surveillance identifies a substantial number of lung cancers at an early stage compared to a control group; • establish whether automated sputum cytometry correctly identifies patients destined to develop lung cancer; • evaluate the malignant potential of pre-invasive lesions; • examine compliance of annual screening. Plan of research: 1568 patients with mild-moderate COPD who are long-term smokers have entered a prospective randomised controlled study. Patients in the surveillance arm will undergo annual sputum cytology/cytometry and, if normal will repeat this investigation annually. Those with abnormal findings will proceed to auto-FB and annual CT. The control group will receive standard clinical follow-up. Both groups will be followed for 5 years.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CANCER AND NEOPLASMS
Title: Cambridge Pancreatic Cancer Centre
Funder: Cancer Research UK

Abstract: The Cambridge Pancreatic Cancer Centre (CPCC) has been set up with the aim of being a centre of multi-disciplinary excellence for the translation of pancreatic cancer research. Our focus is on world class trials of therapies showing effectiveness in research models. We aim to attract patients seeking cutting-edge treatment opportunities. The centre is involved in research ranging from scientific research into the biology of pancreatic cancer, identification of biomarkers, epidemiological studies and clinical trials with the mission of improving outcome for patients with this disease. (http://www.cambridge-pcc.org/index.html).


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: Stratified Health Medicine
Funder: Cancer Research UK

Abstract: This national study aims to identify genetic changes in six cancer types: breast, lung, ovarian, colorectal, malignant melanoma and prostate in a time frame that would make the information useable clinically. The principle is if we can understand which mutations, or “spelling mistakes”, are present in the patients tumour cells’ DNA, and get the results back in a timely manner, this will, in the future, help guide treatment decisions and enable clinicians to tailor drug regimes to an individual’s specific tumour cells (http://www.cuh.org.uk/news/cancer-services/stratified-medicine-programme-changing-face-cancer-research). Nationally, the remit is to recruit 9,000 patients over two years in phase one of the programme. Working with partners such as Papworth, the Experimental Cancer Medicine Centre at Addenbrooke’s aims to recruit 1,100 patients from the six tumour sites. Patients undergoing cancer care will be asked for permission to use surplus tissue taken during routine surgery. Tissue bank staff will then send samples to the technology hub in Birmingham, where DNA will be extracted and tested for a set of specific genetic faults and variations. Any excess DNA will be stored for future ethically approved research projects. Patients may also give consent to have this data used to help build knowledge about the interaction between genes and treatments. How will it benefit patients? The programme is initially concerned with introducing molecular medicine into cancer patient care, as well as facilitating translational research, so scientists and clinicians are trying to improve the technology, the diagnostic techniques and the IT to make this routine in the NHS of the future rather than devising new anti-cancer treatments (drugs) per se. As phase one is a pilot study, it will not affect the way patients are treated but they may help contribute towards research into future treatments. The ultimate outcome, however, is to identify patients who need intensive therapy or will benefit from one of the new targeted therapies and to save patients who have less aggressive tumours from the toxicities of treatments they don’t need, avoid hospital visits and avoid admissions. The selection of the most appropriate treatment for a patient will mean better outcomes, improvement in the quality of life and may also free up clinicians to treat other patients.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Telomere and Genome Stability Group
Funder: Cancer Research UK

Abstract: Telomeres are structures at chromosome ends, consisting of repetitive DNA sequences and associated proteins. They protect chromosome ends from degradation and fusion, both of which cause genome instability similar to unrepaired DNA double-strand breaks. Telomere dysfunction is often associated with the onset of tumorigenesis. The work in this laboratory investigates how factors involved in DNA repair by homologous recombination contribute to the establishment of protective telomeric structures and how they facilitate the successful completion of telomere replication. An important aspect of this work is understanding the DNA damage response emanating from unprotected or damaged telomeres. These studies are extended to analyse how components of the shelterin telomeric complex contribute to telomere protection and tumour suppression.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Immune response evaluation as a prognostic tool in HPV-positive oropharyngeal cancer
Funder: Cancer Research UK

Abstract: Background: The incidence of HPV-positive oropharyngeal cancer has increased significantly over the past 40 years. Patients commonly present with late stage disease, yet studies report significantly better long-term survival in most HPV-positive OPSCC patients compared with those with HPV-negative disease of matched stage. This has led to suggestions that treatment be de-intensified to reduce therapy-related morbidity, and a number of clinical trials are testing this currently. However, within the HPV-positive OPSCC population, there remains a significant minority that respond poorly to treatment and have a poor prognosis (15%). Although smoking has been shown to reduce survival benefit in HPV-positive patients, there is as yet no single clinical or morphological feature for identifying those who will have poor outcome. We have completed a retrospective analysis of a large cohort of oropharyngeal cancer (OPSCC) patients, and found that low levels of tumour-infiltrating lymphocytes (TIL) identify patients with poor survival. We have developed a prognostic model based on TIL-levels, smoking status and tumour size that accurately identifies ‘high-risk’ patients, where the cancer behaves aggressively – an important concern when considering treatment de-escalation. Aims: The purpose of this study is to validate our prognostic model in three independent cohorts of HPV-positive oropharyngeal cancer patients. Methods: We will validate our prognostic model using independent cohorts of HPV-positive orpharyngeal cancer patients from two UK-based NIHR studies, where tissues have been collected prospectively, and also one retrospective Dutch cohort. We will evaluate TIL number, and determine whether levels of serological markers (IgG antibodies against HPV-16 E6 and E7)can also be used independently (in place of TILs) to identify high-risk patients. How the results of this research will be used: Data generated in this study will validate the prognostic model and allow accurate stratification of patients into ‘high-risk’ and ‘low-risk’ groups. This is essential for both individual patient treatment strategies, and entry into future clinical trials that seek to de-escalate treatment in HPV-positive patients.


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

Abstract: 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. 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: Establishing the link between melanoma specific initiating sub populations, autophagy and tumour progression
Funder: Cancer Research UK

Abstract: Cutaneous malignant melanoma is the most aggressive form of skin cancer with an increasing worldwide incidence. Despite recent advances in targeted therapies including vemurafenib, a specific inhibitor targeting BRAFV600E mutated tumours, seen in up to 70% of all melanomas, chemoresistance evolves quickly and clinical outcome remains very poor. Underlying mechanisms of resistance have been proposed but remain to be fully elucidated, thereby emphasizing the acute demand for novel therapeutic strategies for patients bearing both NRAS/BRAF mutant and wild type tumours. Cutaneous melanoma is an extremely heterogeneous human cancer. Evidence from studies in haematological malignancies as well as breast and colon cancer demonstrates the existence of stem-like sub-populations within tumours, which support tumour progression and chemoresistance. In this respect, cancer stem cells may constitute a subpopulation of self-renewing, tumour-initiating cells with the ability to sustain tumour growth. Recently in melanoma, a population of CD271+ and or ABCB5 + cells has been associated with tumour initiation, unlike CD271 and or ABCB5- cells, which are associated with non-malignant melanocytic proliferation. As such, CD271/ABCB5 sub-populations of melanoma initiating cells may represent a target population for novel adjuvant therapy; molecular profiles could be used for the development of precision targeted-therapeutic approaches. However, the mechanism by which these sub populations contribute to melanoma development, progression and chemoresistance remain unknown. The observation that autophagy, the principle catabolic process for the lysosomal mediated degradation of damaged organelles/excess proteins is associated with stem cell maintenance and tumour progression in other cancers leads to the current hypothesis that CD271/ABCB5 +ve melanoma initiating cells utilise autophagy to promote tumour survival and chemoresistance. To test this hypothesis, the aims of this study are to establish the optimal method to isolate CD271/ABCB5 subpopulations from metastatic melanoma cells, correlate expression with autophagic activity and determine their contribution to melanomagenesis in vitro and in vivo through the use of full thickness skin equivalent models and zebra fish melanoma xenografts. Results to these studies will pump prime national fellowship applications to further characterise the contribution of autophagy to melanoma initiating cell-mediated melanoma development, progression and chemoresistance and the definition of novel therapeutic strategies through which to harness autophagy for therapeutic benefit.


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