NIHRDataInsights/HRCSData huggingface dataset:
Title: Targeting the Intestinal Stem Cell Niche through Energy and Metabolism Signalling via the m-TOR for Colorectal Cancer Chemoprevention
Funder: Chief Scientist Office, Scotland

Abstract: Bowel cancer, the second leading cause of cancer deaths in the UK, has a considerable preventable component (~54%). Risk factors include diabetes, obesity, and metabolic syndrome and highlight the strong link between metabolism, diet and bowel cancer. Given the national increase in obesity, we need to understand the ways in which nutrient (food) overload can lead to bowel cancer. We think that excessive nutrients lead to bowel cancer by increasing certain types of cells called stem cells. Cells communicate with each other through signals that tell a cell how to behave. An important regulator of such cell signals is the mTOR molecule, which changes the bowel stem cell response to nutrients to maintain normal activity. The mTOR cell signalling pathway is progressively abnormal in bowel cancer development. We know that common drugs like aspirin and metformin decrease the risk of getting bowel cancer and may decrease stem cells. Hence, there is powerful rationale to study how known bowel cancer preventive agents may reset abnormal metabolism and stem cells. We have previously showed that aspirin blocks the mTOR signal in bowel cancer cells. Our Scottish population data show that aspirin will not prevent bowel cancer in all people taking these drugs and so it is important to identify who will respond so we can get the ‘right drug’ to the ‘right patient’. In this study patients will be given aspirin or metformin or both and blood and bowel lining will be sampled to identify metabolic targets of the drugs and effects on the stem cells. CSO funding will enable us to undertake important metabolic studies to define biomarker response profiles to aspirin and metformin that indicate whether a person may benefit from the cancer prevention properties of these drugs. This research is highly relevant to the long-term goal of bowel cancer prevention, a national health priority research theme.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS
Title: The preclinical optimisation of targeted nanoparticles loaded with beta-emitting nuclides for molecular radiotherapy
Funder: Chief Scientist Office, Scotland

Abstract: Colorectal cancer patients often present with disseminated disease. Whilst radiotherapy is the most effective anticancer treatment for cancers that cannot be surgically removed it cannot be used to control metastatic spread. Currently chemotherapy is the mainstay for treatment of metastases but cancer cells comprising metastases almost always develop resistance to chemotherapy. Molecular radiotherapy involves administering, intravenously, radioactive targeted drugs targeted to cancer cells which seek out primary tumours and metastases and use their radioactive payload to locally irradiate cancer tissue. However the distribution of sufficient cancer cell killing activity throughout a cancer to enable complete destruction of the cancer is problematic due to variation in cancer cell receptor expression and heterogeneity of blood flow. In this project we will produce molecules capable of delivering the necessary high radiation dose to colorectal tumours and their metastases. They will be tested on biological models for efficacy and safety. The results from this study will provide the requisite data for a full clinical study to be submitted to the Medical Research Council.


Research activity codes: 5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Cancer chemotherapeutics and the vasculature-endothelial effects of VEGF inhibitors in vivo in man
Funder: Chief Scientist Office, Scotland

Abstract: Recent developments in chemotherapy, particularly VEGF-inhibitor (VEGFI) drugs, have markedly improved the prognosis of patients with cancer. However, these drugs frequently cause high blood pressure (hypertension) which can lead to heart attacks, heart failure and stroke and can limit their use for cancer treatment. Endothelin-1 is a hormone that causes blood vessels to tighten and may contribute to high blood pressure associated with VEGFI drugs. Blocking the effects of endothelin-1 may therefore reduce or prevent VEGFI-associated blood pressure changes, although this has never been tested in humans. Our long-term goal is to assess the protective effects of endothelin-1 blocker drugs in patients treated with VEGFI. Before doing so, we must better explore whether VEGFIs cause blood vessel narrowing and if endothelin-1 blockers prevent this. We will assess this in healthy volunteers using a special technique called ‘forearm plethysmography’. We will examine the effect of VEGFI on blood flow and also the effect of simultaneous administration of endothelin-1 blockers. These will be given at doses that produce local effects in the arm without affecting the rest of the body. These studies will show whether endothelin-1 blockers may help treat VEGFI-associated hypertension to enable more patients safely to receive vital cancer treatments.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Target radiotherapy of prostate cancer in combination with drugs exploiting the aberrant metabolism of tumours
Funder: Chief Scientist Office, Scotland

Abstract: We intend to refine radiation treatment for prostate cancer which has spread to distant locations throughout the body. Radiation treatment is an important component of the clinical management of prostate cancer which has not spread from the prostate gland. However, there is no cure for prostate cancer which has budded off from the primary tumour and distributed to other sites. To eradicate this aggressive type of disease, we propose to perfect targeted radiotherapy, which uses tumour-seeking drugs attached to radioiodine (131 I). After injection, it binds to the cancer regardless of its situation and irradiates cancerous tissue while sparing normal tissue. A radioactive drug, 131 I-MIP-1095, has recently demonstrated tumour uptake, anti-tumour effects and pain reduction in prostate cancer patients. Its effectiveness will be improved by combination with drugs (radiosensitisers) which increase the susceptibility of cancer cells to radiation treatment. These drugs will target the abnormal metabolism of tumours to selectively enhance the killing induced by the radioactive drug. We propose to determine the most effective combinations of radioactive drug and radiosensitiser.


Research activity codes: 5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Contrast enhanced breast tomosythesis in patients suspected of having breast cancer; a prospective comparsion with the state of the art breast MRI
Funder: Chief Scientist Office, Scotland

Abstract: The most commonly used test to detect breast cancer is a mammogram, a low dose x-ray. This shows most breast cancers, especially in fatty breasts, but when breast tissues are dense (a common normal variation), they can be missed. This means that extra tests like magnetic resonance imaging (MRI) are needed to show if a cancer is present and how big it is. New forms of mammogram have been developed to tackle this problem. Digital breast tomosynthesis (DBT) ‘unwraps’ overlapping shadows and shows distortion caused by slower-growing cancers. Contrast enhanced spectral mammography (CESM) involves injection of a ‘dye’ that highlights the abnormal supply to cancerous tissues in the breast and tends to show faster-growing cancers. It has been shown to work nearly as well as magnetic resonance imaging (MRI), the ‘gold standard’ test for detecting breast cancer. In this study, we are combing DBT and CESM into one test (CE-DBT) and we aim to study how good it is at identifying all forms of breast cancer in women who are attending the outpatient breast clinic with suspicious lumps. If we show that the test works, we could greatly improve patient care by diagnosing breast cancer more quickly and accurately.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Characterisation of the ovarian cancer stem cell niche – targeting stem cell biology to combat drug resistance
Funder: Chief Scientist Office, Scotland

Abstract: Ovarian cancer, the “silent killer” is the most lethal gynaecological malignancy. Many women are diagnosed with advanced disease, when surgery is not possible and combination chemotherapy with drugs called carboplatin and paclitaxel is the most appropriate treatment. Patients often initially respond well, but stop responding as their cancer cells adapt, to avoid being killed by toxic chemotherapy drugs. To better understand why this happens, we have created a unique translational study to compare cancer cells in ascitic fluid obtained from patients as they progress through treatment and become resistant to chemotherapy. Intriguingly, our data suggests that resistance results from chemotherapy-induced expansion of small numbers of inherently resistant, immortal “stem cells”, with specialised survival properties which work together to promote drug resistance. Excitingly, if we can better understand these processes, we may be able to use highly specific novel combination treatment approaches to target and disable them, re-sensitising chemotherapy resistant cancers


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: IMAGE-INE – analysing IMAGE guidance scans to predict late toxicity after radiotherapy in head and neck cancer patients
Funder: Chief Scientist Office, Scotland

Abstract: Cancers of the head and neck are increasing. Advanced radiotherapy (RT) techniques cure most patients, but permanent side effects are common, and can be severe. Adapting (changing) radiotherapy plans (ART) by altering the dose or target treated during the 6 week course of therapy could reduce side effects while maintaining excellent cure rates. However, we don’t yet know how, or when, to select patients for ART. Recent research using sophisticated image analysis techniques shows that features in pre-treatment CT scans, i.e. done before treatment, can partly predict late toxicity. Modern radiotherapy machines can take image guidance (IG) CT scans immediately before each daily treatment. Because they are taken daily during a course of therapy, we believe these on-treatment images will give more predictive information about individual response. Our project will look for features that predict toxicity, to identify patients in whom ART may improve their quality of life.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Staging by Thoracoscopy in potentially radically treatable non-small cell lung cancer associated with minimal pleural effusion
Funder: Chief Scientist Office, Scotland

Abstract: Early-stage Non-Small Cell Lung Cancer (NSCLC) can be cured by ‘radical treatment’, which involves either major surgery or combination radiotherapy and chemotherapy. However, up to 50% of radically-treated patients die within 2 years and suffer major side-effects. When a rim of fluid surrounds the lung at diagnosis (called Minimal Pleural Effusion (MiniPE)) recurrence risk is extremely high. Earlier studies based on review of lung cancer databases in S. Korea, Spain and Scotland suggest that MiniPE may reflect incurable metastases on the lining of the lung (pleura) in up to 80% of patients. However current staging tests, including scans such as CT and PET-CT, and simple needle sampling of the pleural fluid frequently miss these. We will perform Local Anaesthetic Thoracoscopy (LAT) in 96 patients with MiniPE and an otherwise radically-treatable NSCLC. LAT involves insertion of a thin telescope into the pleural space under local anaesthetic. LAT is well-tolerated, accurate and safe in larger pleural effusions but has not been used to stage lung cancer before. If LAT proves accurate and safe in THIS setting it could help select curable patients for radical treatment, and protect others from unnecessary risks.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Development of personalised medicine approaches for the clinical application of IAP antagonists in metastatic and high risk early stage colorectal cancer
Funder: Department for the Economy, Northern Ireland

Abstract: We are continuing to develop clinical decision making tools for the treatment of bowel cancer patients in the advanced disease settingwhen very limited treatment options exist. We are focussing on a new type of treatment that induces both tumor shrinkage andactivates the immune system to boost this effect. These drugs are currently in clinical trials. However not all patients will respondequally, and we have developed diagnostic tools that can identify those patients that may respond.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Metabolomic and array based biomarker approaches to understand human exposure to potent carcinogenic fresh water toxins
Funder: Department for the Economy, Northern Ireland

Abstract: The presence of harmful algal-toxins in drinking water is becoming more prevalent and drinking water is becoming more scarce. Thereis a proposed link between toxin exposure and the development of cancer, specifically colon and liver cancer. Currently, there is nomethod to measure toxin exposure or the impact that exposure has on cancer progression. Therefore, it is impossible to know howimportant toxin exposure is in these diseases. We will identify indicators of toxin exposure and develop a test to assess whetherindividuals are at risk from cancers as a result of chronic toxin exposure to harmful algal toxins.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS
Title: Protein Biomarker Arrays for the Personalised Treatment of Prostate Cancer
Funder: Department for the Economy, Northern Ireland

Abstract: The aim is to develop a novel test regime that will allow the detection of prostate cancer with a far higher degree of accuracy than is currently available. The core objectives involve the development and validation of prototype electrochemical sensors that incorporate a panel of molecular recognition components which simultaneorsly target a range of biomarkers associated with the disease.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Minitub: Prospective registry on Sentinel Node (SN) positive melanoma patients with minimal SN tumor burden who undergo Completion Lymph Node Dissections (CLND) or Nodal Observation
Funder: Friends of EORTC

Abstract: With this prospective registry we aim to evaluate the outcome of patients with a T2-T3 primary melanoma and minimal SN tumor burden, treated by CLND or nodal observation: ♦ The main objective is to determine if T2-T3 melanoma patients with minimal SN tumor burden and managed by nodal observation have a 5-year DMFI comparable to similar patients (T2-T3 melanoma patients with minimal SN tumor burden) treated by CLND based on historical data from the literature. We will compare this with SN-negative patients, based on historical data as well. ♦ We will also determine the actual proportion of patients and their characteristics, who opt to undergo a CLND compared to those, who opt to undergo nodal observation.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: CANCER AND NEOPLASMS
Title: Trabectedin for recurrent grade II or III meningioma: a randomized phase II study of the EORTC Brain Tumor Group
Funder: Friends of EORTC

Abstract: The aim of this randomized phase II study is to collect data on activity, safety and quality of life of trabectedin therapy in patients with recurrent high-grade meningioma.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Genetics of EGFR Mutation Study (GEM): a Translational Study of the EORTC Lung group
Funder: Friends of EORTC

Abstract: Objective 1: To identify germline allelic DNA variation associated with somatic EGFR mutation in NSCLC, Objective 2: Correlation between germline allelic variants and survival in EGFR somatic mutant NSCLC. Objective 3: Study germline allelic DNA variation associated with never /ex light smoking NSCLC. Objective 4: Catalogue distribution of somatic EGFR mutant genotypes in 1,000 EGFR mutant NSCLC cases and describe their relationship to clinical outcome.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Randomized trial assessing the significance of Bevacizumab in recurrent grade II and Grade III gliomas. The TAVAREC trial
Funder: Friends of EORTC

Abstract: Primary objective: activity of both the combination TMZ plus bevacizumab and TMZ alone in recurrent grade II or grade III glioma patients without 1p/19q co-deletion ♦ Secondary objectives: safety, patient-oriented assessment of clinical benefit ♦ Exploratory objectives: qualification or discovery of prognostic and/or predictive biomarkers of activity or efficacy. Discordances between RANO and Macdonald's criteria.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Development and validation of the EORTC computerized adaptive testing (CAT) instrument - Project Extension
Funder: Friends of EORTC

Abstract: To optimize measurement precision and flexibility a computerized adaptive test version of the EORTC QLQ-C30 has been developed. In CAT assessment, the selection of items is tailored to the individual based on responses to prior items. Item banks, from which the CAT selects items, have been developed for all symptom and functional domains of the QLQ-C30. These each comprise between 7-34 items and the new instrument comprises a total of 262 items. Evaluations indicate higher measurement precision and thereby increased statistical power of the CAT compared to the QLQ-C30. Thus, using the CAT, sample sizes may be reduced by approximately 20-35% on average without loss of power.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Development of thresholds for the EORTC QLQ-C30 and the EORTC CAT measures to enable their use for symptom screening in daily clinical practice
Funder: Friends of EORTC

Abstract: To improve interpretation of patient-reported outcome (PRO) data collected with the EORTC QOL measures the project develops thresholds for clinical importance. These thresholds will facilitate interpretation of QOL scores collected in daily clinical practice and of trial results.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS
Title: Putting hidradenitis suppurativa on the NHS map: antibiotic stewardship, epidemiology and core outcome domains
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Hidradenitis suppurativa (HS) is a long term skin condition involving multiple boils in skin creases such as the arm pits, groin and genital region. The boils are very painful, discharge pus and result in disabling scarring. HS is hidden from view and embarrassing and so has been neglected by medical research and society in general, despite affecting about one in 100 adults. Most patients are managed by GPs with multiple short courses of antibiotics, sometimes over 100 courses, which do not help with the skin boils and will increase the risk of antibiotic resistance. This fellowship will lay the fundamental building blocks to guide future HS research. A more accurate estimate of how common HS is will be obtained from routinely collected GP data from a Welsh and a UK databank. Antibiotic prescribing patterns will be examined before and after the diagnosis of HS appears in the electronic GP record to see if recognition of the condition reduces inappropriate antibiotic prescribing. The Welsh databank will be used to quantify healthcare resource consumption, including A&E attendances for incision and drainage of boils. We are still understanding how best to define treatment success or failure for HS. This is fundamental to the design of HS clinical trials. A consensus process will be conducted between patients and clinicians to define core outcomes that should be included in all future HS trials. This will ensure that the patient perspective, for example pain reduction, is central when evaluating whether a treatment has been successful. It will also permit different treatments for the condition to be compared. This fellowship offers the chance to put a neglected, relatively common, painful and embarrassing condition on the Welsh NHS map and will establish Wales as an international leader in HS research and patient care.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CANCER AND NEOPLASMS
Title: Functional characterisation of EFA6R, a possible biomarker for ovarian cancer
Funder: Health and Care Research Wales (Welsh Government)

Abstract: The ovaries, situated on both sides of uterus, are the organs that produce eggs. Cancer that forms in ovarian tissues is called ovarian cancer. Age, race, infertility, family history of ovarian cancer and personal history of breast or colon cancer increase the chances of getting ovarian cancer whereas pregnancy, oral conceptive use and hysterectomy reduce the chances of getting ovarian cancer. Ovarian cancer is commonly diagnosed in women 55 or older and rarely in women under 30. White women are affected slightly more often than black women. Women suffering from infertility have about a 2-fold higher ovarian cancer risk than does the general population. Unfortunately ovarian cancer is lethal because most of the cases are detected in advanced stage of the disease. Only about 20% of the patients with advanced stage of disease will survive 5 years or longer. However, if the disease is detected in its early stage, then 90% of patients can be cured with surgery and drugs. So the detection of ovarian cancer in early stage would greatly reduce ovarian cancer associated deaths. Unfortunately there are no reliable screening methods available currently to detect ovarian cancer in its early stage. So there is an urgent need for identifying screening methods to diagnose ovarian cancer at an early stage. EFA6R is a novel protein and its levels are reduced in ovaries before they become cancerous.


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