NIHRDataInsights/HRCSData huggingface dataset:
Title: Prostate Cancer: High Accuracy Early Diagnosis based on Tissue Microenvironments
Funder: Cancer Research UK

Abstract: Background: Prostate cancer (PCa) is the most common cancer in men in the UK, and as the population ages, the number of cases will continue to increase. Unfortunately, there are limitations in the accuracy of tests currently available to diagnose PCa, and in some cases the tests provide conflicting information. For example, high quality images taken using Magnetic resonance imaging (MRI), may suggest cancer is present, whilst prostate biopsy results are non-cancerous. As a consequence, it is not always clear if or how we should treat men, or whether we should monitor with blood tests and high quality image scans using MRI. Therefore, any method of improving our ability to detect PCa early and further, to help decide whether a patient requires treatment or just monitoring, is an extremely important area of research. Recent studies have suggested X-ray scattering measurements (which provide information on the composition of a material), are different between normal healthy tissue and cancer, and in specific cases, for example breast cancer, may even be different between high and low risk cancers. Aims: This project aims to evaluate how X-ray scattering patterns change in prostate cancer tissue. This will provide an understanding on chemical changes that occur in the tissue due to the presence of cancer. It is hoped that these chemical changes can provide an earlier, more accurate diagnosis of PCa cancer. Methods: Tissue from prostate biopsies will be analysed using X-ray scattering techniques, and other complementary scientific techniques including infrared spectroscopy. Non-cancerous, low and high grade cancerous tissue, and tissue in cases were clinical tests provided conflicting results, will be analysed. This will provide an in-depth understanding of chemical changes to the tissue across a range of tissue types. How the results will be used: With few studies in this research area, it is anticipated we can improve our understanding of the chemical changes that occur in prostate tissue due to the presence of cancer. We will investigate whether patterns of X-ray scattering are different in non-cancerous, high and low risk prostate cancer tissues. These results will be used to inform our analysis and interpretation of ‘ambiguous’ tissue specimens, were current tests (imaging and biopsy) provided conflicting results. This will allow us to determine whether tissue chemistry can provide a useful additional method of early detection for PCa, which would be particularly useful in cases were current clinical tests provide conflicting results.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: EDPan Screening tool - Earlier detection of pancreatic cancer through personalised assessment of risk combined with non-invasive infrared spectroscopy
Funder: Cancer Research UK

Abstract: Background Pancreatic cancer has one of the poorest survivals of all cancers, which is partly attributable to advanced disease stage at diagnosis. Diagnostic delay occurs because symptoms are non-specific. Screening programmes to identify individuals at a high-risk of pancreatic cancer are needed to prioritise people for diagnostic screening. Clinical risk factors can identify higher-risk individuals but are not specific enough alone, so require follow-up with a minimally invasive, sensitive, and specific diagnostic test. Aims This feasibility study will assess the ability of a non-invasive personalised screening strategy (EDPan) to identify individuals with pancreatic cancer. The EDPan strategy will combine clinical and demographic information with infrared spectroscopy-based analysis of serum and urine samples, together with immune profiling. Specific aims include: a) To perform high throughput assessment of the systemic response to cancer using ATR-FTIR spectroscopy profiling in serum and patient-matched urine samples. b) To refine the spectroscopy prediction tool by evaluating cytokines and immunoglobulins within the same samples. c) To externally validate a risk prediction algorithm (QCancer®), using data from the UK Biobank and AMORIS cohorts, to support identification of patients to prioritise for blood/urine testing. These will be further validated within individuals with non-specific symptoms, new-onset diabetes (a high-risk group for pancreatic cancer), or pancreatic cancer using baseline information included in the ADEPTS and PANDIA cohorts. Methods We will analyse samples from individuals with and without cancer, within the ADEPTS and PANDIA cohorts, using a high throughput liquid biopsy platform technology called ATR-FTIR spectroscopy, combined with machine learning. ATR-FTIR spectroscopy will be aligned with immune profiling using a customised array where 64 selected cytokines will be measured per patient together with a set of specific immunoglobulins. We will assess discrimination and calibration of the QCancer® tool for identifying individuals at a high-risk of pancreatic cancer within 5 years using data from the UK Biobank and AMORIS. We will subsequently assess the discriminative ability of ATR-FTIR spectroscopy analysis alone and in combination with clinical risk factors and immune data. How the results of this research will be used The EDPan tool is intended to support triage of non-symptomatic and symptomatic patients at high-risk of PDAC for rapid access to diagnostic interventions. The results will inform the development of larger studies to assess the utility of a screening pathway that first identifies individuals at a higher risk of pancreatic cancer within 5 years using clinical risk factors, and then uses ATR-FTIR spectroscopy.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Cancer Led Optical Ultrasound Detection
Funder: Cancer Research UK

Abstract: One of the most difficult problems when treating cancer is how different each cancer type is - different tumours express different proteins in different amounts, respond differently to different treatments and so on. It is not unfair to say that there is no one disease called cancer; it is a family of, often very different, diseases. That said, one of the few things that all solid tumours need is a source of nutrients and oxygen, and a way to get rid of waste. This means growing new blood vessels, and tumours do this by releasing chemicals that cause blood vessels to grow. As one might expect, when blood vessels grow in response to a tumour, they don't do so in a nice, orderly way. The resulting blood vessels are often leaky, follow a tortuous path, or the blood flow can be abnormally slow. In some cases the blood can be stagnant, or even flow in two different directions. One way to examine these unusual flow patterns is to use ultrasound - particularly a technique called Doppler-mode ultrasound. This is sensitive to moving things (like blood) but normal ultrasound scanners aren't well suited to searching the body for abnormally-structured blood vessels. They must be steered by hand, have a limited field of view, and the image quality isn't good enough for the smallest blood-vessels. This is where Cancer-Led Optical Ultrasound Detection (CLOUD) comes in. As the name implies, CLOUD is an optical way of doing ultrasound imaging. It projects light onto a special layer of material which converts that light into sound waves. These sound waves are then reflected and cause the surface of the material to vibrate. These vibrations can be measured by bouncing another laser beam off the material surface, and using a phenomenon called interference to measure the position of the surface down to the nanometer. A special high-resolution camera can then take pictures of this interference pattern to work out how the surface is vibrating in response to the reflected ultrasound. Ultimately, CLOUD will be used to scan the whole body, looking for regions where the blood flow is unusual, and ascertaining whether they need further investigation. Given that this is a very long-term goal, the purpose of this project is to try out some of the riskier technologies to see if they can be made to work.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Early cancer diagnostics and stratification based on nucleosome positioning reconstructed from cell-free DNA
Funder: Cancer Research UK

Abstract: Background. Liquid biopsy approaches of diagnostics and patient monitoring based on cell-free DNA (cfDNA) are becoming a very promising direction and have already entered the clinic. As opposed to conventional biopsies of solid tissues, liquid biopsies are based on the analysis of blood plasma, urine and other body liquids, which can provide less invasive, more sensitive and more affordable tests. However, current cfDNA assays are mostly based on the analysis of DNA mutations (the first generation of liquid biopsies) or methylation (second generation). Both these types of markers are less prevalent in cell-free DNA at early stages of cancer development. Thus, the challenge to develop sensitive and cost-effective cfDNA analysis for early diagnostic is still open. Aims. To address this challenge, here we will develop a third generation of cfDNA analysis based on computational reconstruction of nucleosome positioning landscapes. We hypothesise that alterations in nucleosome repositioning occur earlier in cancer development compared to other markers such as DNA mutations or methylation, and thus can provide more sensitive diagnostics. Methods. Our previous work devoted to nucleosome repositioning in cancer, as well as recent preliminary investigations using cfDNA datasets from our NucPosDB database as well as patient data from collaborators showed that we already have a working approach allowing reconstructing nucleosome positioning landscapes from cfDNA and using these for patient diagnostics and stratification. Our method allows distinguishing different cancer types, subtypes and susceptibility to anticancer drugs. In this project, we will scale up this investigation to expand to more conditions, improve diagnostic precision by including more sequenced datasets, and provide molecular connection between cfDNA and chromatin in the cells of origin to aid personalised therapy. To do so, we will first train our model using nucleosome positioning generated in the current project in paired normal/tumour brain tissues and cfDNA from the same glioblastoma patients, then will expand it to other cfDNA datasets from published sources, and finally develop a prototype version of the clinically applicable software for cfDNA nucleosomics-based diagnostics. How the results of this research will be used. Upon successful completion of the current project our method of cancer diagnostic and stratification will be suggested for clinical trials for cancer subtypes profiled in the current project, as well as larger-scale projects focusing on new cancer types, such a breast cancer, prostate cancer and lung cancer, for which we will perform preparatory work here.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Recapitulate the initiation and progression of Barrett’s oesophagus using patient-derived organoids
Funder: Cancer Research UK

Abstract: Background Oesophageal adenocarcinoma (OAC) is a highly lethal cancer and increasing across western countries; it has a poor prognosis with an overall five-year survival rate of 15%. OAC originates from a precursor lesion, known as Barrett’s oesophagus (BO), which has well defined histopathological stages: intestinal metaplasia, low- and high-grade dysplasia and eventually to cancer. BO is commonly associated with long term acid reflux and bears high mutation burden. Although great effort has been made using advanced sequencing technologies to delineate its genetic and epigenetic profiles, the precise mechanism of initiation, development and malignant transformation of BO remains unclear, which is largely due the lack of a robust and accurate models that allows in vitro studies. Aims We aim to establish patient-based in vitro models to understand: 1) how mutations are acquired prior to BO development; 2) how BO progression and malignant transformation is influenced by environmental factors; and 3) which normal cell/tissue type is more susceptible to such changes. Methods We have established a number of human organoid lines derived from patients as well as disease-free organ donors, which include normal gastric organoids from GOJ region and gastric body, BO organoids from IM and dysplasia. The organoid lines will be treated with various environmental factors and subsequently sequenced for their transcriptomic, genetic and epigenetic changes. How the results will be used The project will provide a comprehensive patient-based platform that allows functional validation of environmental factors, mutagens and critical genes that involved in BO development and progression. The result will be used to provide an experimental basis for early detection and risk stratification of BO/OAC patients.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Scottish Obesity Alliance
Funder: Cancer Research UK

Abstract: Background Obesity continues to be a significant public health challenge in Scotland with 29% of adults and 16% of children being obese. Being a healthy weight is the second most important thing after smoking that individuals can do to prevent cancer. People keeping a healthy weight could prevent around 22,800 cases of cancer every year in the UK. The Scottish Obesity Alliance (SOA) brings together 27 organisations from across Scotland who have an interest in obesity prevention. SOA have already had considerable success in their short lifetime (est. 2017) of influencing the need for a Food Promotions Bill in Scotland, drawing attention to the inequalities issues facing children in relation to obesity and influencing planning system policy. All of this work will positively impact on obesity prevention. Aims The aim of this proposal is to continue to operate, develop and expand the Scottish Obesity Alliance. We aim to continue to focus our work on three strands: • Advocacy and communication • Identifying policy-relevant evidence and solutions • Sharing knowledge and evidence between members We are aiming to further capitalise on our position by providing unique advocacy voices that bring strength in the depth and breadth of SOA members. Methods Our future work will focus on the following specific outputs: 1. Youth advocacy platform on obesogenic environment issues 2. Turning the Tide: A set of Scottish recommendations from the OHA report and accompanying advocacy plan 3. NPF 4 consultation responses and advocacy plan These outputs will be used to influence the following key policy initiatives that we know are currently in process or proposed within Scotland: • National Planning Framework 4 – a unique chance to influence built environment policy across Scotland in terms of food and physical activity environments. • Public Health Bill – the commitment of Scottish Government to a Public Health Bill provides us with the opportunity to ensure that the existing commitment to tackle promotions of unhealthy foods is progressed but also the opportunity to consider other marketing issues What value will the programme of work deliver? Tackling obesity requires system wide change. We believe the Scottish Obesity Alliance through its wide membership, knowledge breadth, dynamic and agile outlook and advocacy reach can effect change across a wide number of issues and with a wide audience. Our work will influence Scottish Government and Scottish Parliament to implement the system change required to achieve population wide healthy weight.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: CANCER AND NEOPLASMS
Title: Obesity Health Alliance: Core Funding
Funder: Cancer Research UK

Abstract: Excess bodyweight increases the risk of several serious health conditions including 13 different types of cancer. Having obesity is the single biggest preventable cause of cancer in the UK after smoking, and is linked to 13 different types of the disease. The Obesity Health Alliance (OHA) brings together a wide range of organisations and expertise under a strong coalition including 44 major health charities, medical royal colleges, campaign groups and grassroots organisations. The alliance works together on a programme of activity by developing detailed policy positions, influencing key decision makers in parliament and Government and using the media to raise the profile and build public support for action to tackle obesity. The OHA operates in the following ways: • Sharing insight and expertise among members • Developing and advocating evidence-based policy recommendations • Influencing decision makers and the media The OHA’s advocacy work is framed around a ten point policy position statement, outlining the ten policy calls we collectively believe will be most effective in tackling obesity, which all alliance members support. This statement is reviewed every two years via an extensive mapping and member engagement process to ensure it reflects policy goals of our members and capitalises on existing policy windows. Of the ten policy areas, the OHA steering group sets three policy priorities. These are currently as follows: 1) implementation of an ambitious reformulation programme; 2) greater protection for children from junk food marketing; 3)introduction of restrictions on HFSS price and place promotions in the retail and out of home sectors. The core work of OHA is geared around progressing these policy priorities by researching and developing policy positions and communicating these to policymakers via public affairs and media activity. Over the next two years OHA will also be leading a process to develop an independent obesity strategy. The OHA’s advocacy plans build on the successful foundations of the alliance to date and align closely with Cancer Research UK’s plans. A continuation of Cancer Research UK’s key role in the OHA will mean that activity can continue to be closely aligned with Cancer Research UK’s campaign activity on obesity, with the OHA activity designed to amplify and complement the charities efforts and working closely together to identify areas where consensus and a strong collective voice will be most effective in advocating for change.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CANCER AND NEOPLASMS
Title: CRUKD/17/009 A first in class, first in human Phase I clinical trial of the MT1-MMP-directed bicyclic peptide drug conjugate (BDC) BT1718 in solid cancers including NSCLC, sarcoma and TNBC
Funder: Cancer Research UK

Abstract: MT-1-MMP is a matrix metalloproteinase that is over-expressed in numerous solid tumours including NSCLC, TNBC and soft tissue sarcoma. BT1718 is a first-in-class bicyclic peptide with a linker and DM-1 cytotoxic payload that is in preclinical development. BT1718 has shown to have growth in multiple xenograft models (lung, breast and sarcoma). Bicyclic peptides linked to a chemotherapy payload are different from antibody-drug conjugates as they have rapid tumour penetration and a large volume of distribution and shorter half-lives with a renal clearance which reduces toxicity. The current project involves development of BT1718 in a partnership between CDD and Bicycle Therapeutics. The development will include preclinical experiments to study detailed preclinical toxicity to enable a phase I study. Other areas of preclinical research include validating an IHC assay to detect MT-1 expression. In addition, tissue microarrays of multiple tumour types will be studied to find additional indications. Patient-derived xenografts will also be used to study the effect of the drug in different clinical settings to further refine the clinical hypothesis. The clinical studies will include a dose escalation cohort and a dose expansion cohort. The primary objective of the dose escalation cohort of the phase I study is to recommend a phase II dose and to study clinical toxicities, including dose limiting toxicities. Secondary objectives include the study of the pharmacokinetics of BT1718. A tertiary objective would be to study pharmacodynamic biomarkers of response in pre- and post-tumour biopsies. It is estimated that 35 - 40 patients will be recruited in to the phase I study. Once a phase II dose is recommended, following the dose escalation up to three dose expansion cohorts will be studied. The current planned target populations include MT-1 expressing NSCLC, TNBC and soft tissue sarcoma. However, different disease cohorts may be prioritized if new preclinical data emerges.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS