NIHRDataInsights/HRCSData huggingface dataset:
Title: CRUK/14/020: Tracking Cancer Evolution through Therapy (Tracer X)
Funder: Cancer Research UK

Abstract: Prospective observational cohort study in primary NSCLC. 842 patients with stage I-IIIA NSCLC will be recruited and followed up for 5 years. To study the NSCLC genomic landscape between primary and metastatic sites and the evolutionary dynamics of intratumour heterogeneity over time combined with detailed clinical, histopathological and cancer phenotypic annotation for each patient, in order to significantly improve the outcomes of NSCLC patients (e.g. reduce their chance of recurrence and improve survival). Primary objectives: • Define the relationship between intratumour heterogeneity and clinical outcome (disease-free survival and overall survival) following surgery and adjuvant therapy (including relationships between intratumour heterogeneity and clinical disease stage and histological subtypes of NSCLC). • Establish the impact of adjuvant platinum-containing regimens upon intratumour heterogeneity in relapsed disease compared to primary resected tumour. Secondary objectives: • Development and validation of an intratumour heterogeneity ratio index ITB as a prognostic or predictive biomarker in relation to its association with DFS and OS • Infer a complete picture of NSCLC evolutionary dynamics: Define drivers of genomic instability, metastatic progression and drug resistance by identifying and tracking the dynamics of somatic mutational heterogeneity, and chromosomal structural and numerical instability present in the primary tumour and at metastatic sites. Individual tumour phylogenetic tree analysis will: a) Establish the order of somatic events in relation to genomic instability onset and metastatic progression b) Decipher genetic “bottlenecking” events following metastasis and drug therapy c) Establish dynamics of tumour evolution during the disease course from early to late stage NSCLC. • Initiate a longitudinal minimally-invasive circulating tumour cells (CTC) and cfDNA biobank to develop analytical methods for the early detection and monitoring of tumour evolution over time. • Develop a longitudinal tissue resource to serve as a platform to assess the relationship between genetic intratumour heterogeneity and the host immune response. • Develop a repository of lung cancer organoids and in vivo mouse models of patient-derived lung cancers that can be used as in vitro and in vivo models to predict response to therapeutics and resistance. • Define relationships between intratumour heterogeneity and targeted/cytotoxic therapeutic outcome. • Through UCL-GCLP gene panel in a certified laboratory environment, TRACERx will define clonally dominant disease drivers to address the role of clonal driver dominance in targeted therapeutic response, and to guide stratification of lung cancer treatment.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Cancer Research UK ICR Centre
Funder: Cancer Research UK

Abstract: The Institute of Cancer Research (ICR) and Royal Marsden NHS Foundation Trust (RM) are unique within the CRUK Centres and ECMC networks as the only university and NHS hospital partnership, and the sole NIHR Biomedical Research Centre (BRC), dedicated purely to cancer research and treatment. We have a strong track record in cancer biology and genetics; drug discovery and clinical development; advancing and disseminating improved radiotherapy techniques; and the clinical application of genetic information, utilising this for better prevention and targeted screening for earlier diagnosis. We have driven understanding of cancer cell signalling, three-dimensional structures of key cancer proteins, cancer predisposition genes and synthetic lethal therapeutic strategies and we have pioneered the study of cancer complexity and adaptability, showing that cancers evolve and diversify, becoming treatment resistant, in a Darwinian fashion by natural selection. Our Centre will support four key themes within our research strategy and that of CRUK. The Image-Guided Therapies Theme will develop more effective local treatments, improving patient survival and quality of life by applying advanced imaging technologies to guide radiotherapy, surgery and ablative modalities, including High Intensity Focused Ultrasound (HIFU). This will include the development and evaluation of innovative technology integrating diagnostic image-quality MR scanning with a linear accelerator (MR Linac) for real time treatment adaptation. The Systemic Therapies Theme, and the closely integrated activities of the ECMC, led by the Drug Development Unit (DDU), will focus on developing novel therapeutic strategies and conducting investigator-initiated trials, including the study of innovative drugs discovered in the CRUK Cancer Therapeutics Unit. We aim to discover at least five mechanistically novel drug candidates over the next 5 years, including first-in-class agents designed to overcome cancer evolution and drug resistance and the DDU will take successful candidates into hypothesis-driven, biomarker-led, first-in-human. The Big Data Theme will build on our leading position in multidisciplinary Big Data integration and predictive analytics to innovate data mining and machine- and deep-learning technologies. We will apply these in reiterative clinical-discovery research to develop evidence-based, decision-support tools and adaptive precision treatment approaches including novel combinations. Together, these Centre activities will help CRUK to deliver its strategy to ‘Continue to discover and develop new therapeutics, surgery and radiotherapy treatments’. In the Cancer Discovery Science and Infrastructure Theme, we will elucidate mechanisms of oncogenesis, with increasing focus on genetic instability and cancer evolution. Through this we will support translation by the identification of new therapeutic targets and biomarkers.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Cambridge CRUK Major Centre
Funder: Cancer Research UK

Abstract: The Cancer Research UK Cambridge Centre will bring together the diverse strengths of Cambridge to create novel practical applications that will improve the detection and treatment of cancer. The Centre will develop programmes in early detection, and integrative cancer medicine with the aim of developing new therapeutic approaches (http://www.cruk.cam.ac.uk/).


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: CANCER AND NEOPLASMS
Title: Manchester CRUK Major Centre
Funder: Cancer Research UK

Abstract: Research at the CRUK Manchester Institute spans the whole spectrum of cancer research, from programmes investigating the molecular and cellular basis of cancer, to those focused on translational research and the development of novel therapeutic approaches. The Institute works in close collaboration with The Christie and is a partner in the Manchester Cancer Research Centre. Our aim is to gain a greater understanding of the fundamental basis of how cancer develops and apply that knowledge to develop new diagnostic tests, potential treatments and better ways to predict the outcomes. We have first class translational research facilities to support current activities and develop into new areas such as molecular pathology. One of the laboratories meets Good Clinical Laboratory Practice standards, and this improves our ability to assess clinical samples from early phase trial patients under the strict regulations which are now required.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: CANCER AND NEOPLASMS
Title: Cancer Research UK Cancer Therapeutics Unit
Funder: Cancer Research UK

Abstract: Over the next quinqunium we will undertake a portfolio of research projects that will encompass early stage target validation, through to discovery and development of compounds that will undergo proof of concept clinical trials. In addition we will utilise essential underpinning technologies that are critical to our discovery of novel chemical tools and preclinical developmental candidates. Our focus will be on small molecule approaches to address the challenge of tumour evolution, heterogeneity and drug resistances by focusing on four Research Themes which include: 1. Non-oncogenic addiction 2. Genomic Instability 3. Tumour-host interactions 4. Cellular State and Plasticity An important aspect of our drug discovery programme will be to identify new targets and drug resistance mechanisms based on the genetic and molecular characterisation of human cancers, supported by computational biology and chemogenomic approaches to assess drugability. We will also aim to target difficult to drug target proteins using E3 Ligase mediated degradation approaches. We will exploit our close working relationship with The Royal Marsden Hospital to reverse translate observations in the clinic for drug discovery. Our overall objective over the next quinquenium will be to discover at least 3 pre-clinical candidates for subsequent hypothesis testing in Phase I clinical trials and to publish our science in relevant leading journals. Through our drug discovery and development work we will put a greater emphasis on generating a preclinical package that defines sensitive patient populations and predictive biomarkers that will enable more rapid and effective clinical progression. We will continue to train and mentor the next generation of drug discovery scientists through our PhD training programme and well as clinical and non-clinical Post Doctoral Fellowships.


Research activity codes: 5.1 PHARMACEUTICALS;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Bimodal Electric Tissue Ablation: First-in-Person Clinical Study
Funder: Innovate UK

Abstract: Colorectal cancer is the second most common cause of cancer-related deaths in Europe and North America, after lung cancer (Jemal et al., 2007). In the UK, approximately 34,500 new cases of colorectal cancer and 16,200 deaths were registered in 2001 (Cancer Research UK, 2005). This equates to 1 death in the UK from colorectal cancer every 32 minutes. About 70% of patients with colorectal cancer develop secondary malignant growths in the liver, known as colorectal liver metastasis (CLM; Rothbarth et al., 2005). Overall life expectancy is mainly determined by progression of CLM, rather than the primary cancer (Paschos and Bird, 2008). Without treatment, life expectancy with CLM is less than 1 year (McMillan et al., 2007). Surgery to remove the entire metastasis is the only current hope of cure in CLM. Yet, 80% of patients with CLM are not suitable for surgery (NCCN guidelines, 2016), either because of the tumour's location (close to major blood vessels or bile ducts), or because the patient has limited liver function, or is considered high surgical risk (e.g., because of their age). Thermal ablation is a promising CLM treatment, which relies on localised heating to destroy tumour cells. Most commonly, the heat is generated by radiofrequency alternating current (AC). However, radiofrequency ablation is only suitable for CLM with ? 5 lesions and tumour sizes < 3 cm in size (Crocetti et al., 2010). It is challenging to limit tissue heating and avoid charring and vaporisation (Guenette and Dupuy, 2010). Ablatus was founded in 2015 and is the first spin-out from Norfolk and Norwich Hospital. Our novel technology, known as Bimodal Electric Tissue Ablation or BETA, was invented by Dr John Cockburn and Dr Simon Wemyss-Holden (Cockburn et al., 2007) and is now wholly owned by Ablatus. BETA is a disruptive and game-changing innovation that goes significantly beyond current state-of-the-art ablation techniques. We combine AC radiofrequency ablation with direct current (DC). DC induces water flow from surrounding tissues to the ablation site, protecting the tissues from desiccation, enabling much larger tumours to be treated, as well as potentially enabling ablation of previously untreatable tumours, with fewer adverse patient impacts, at a lower cost to the NHS. This project builds on the successful delivery of Ablatus' previous Innovate UK project with eg technology (103351) and will support further collaborative prototype development between Ablatus and eg technology, culminating with first-in-person trials of our device with Addenbrooke's Hospital.


Research activity codes: 5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Scalp cooling for the prevention of chemotherapy-induced alopecia: increasing patient access through eco-design and innovative manufacturing.
Funder: Innovate UK

Abstract: Chemotherapy-induced alopecia (CIA)/hair-loss is widely recognised as one of the most traumatic side-effect of chemotherapy treatment. Without treatment CIA affects 3.5 million patients worldwide and over 67,000 in the UK annually. Scalp cooling is recognised as the only effective treatment for CIA prevention. SME, Paxman Coolers Ltd., are the global leaders in scalp cooling, active in \>63 countries they dominate the market with an 80% share. The demand for machine-based scalp cooling has exponentially increased year-on-year since 2017, when the Paxman Scalp Cooling System (PSCS) achieved FDA approval. Recent international clinical recommendation drives increased demand for machine-based scalp cooling, with Clinical Practice Guidelines revised to include scalp cooling for cancer care in the USA (NCCN 2019/2020), Europe (ESMO 2020) and Australia (CancerAustralia2020). In the USA, following recent publication of 2 x CPT codes (AMA:2021) broader insurance coverage/payment is expected within 2-years which will further increase US-demand as treatment becomes financially viable for more patients. Building on previous successful collaborations, this project will bring together, **Paxman Coolers Ltd**, and the medical-design expertise of the **University of Huddersfield**'s award-winning product design team and technical material research. Through innovative, advanced design and development, this project will dramatically increase patient and clinical access to effective scalp cooling treatment internationally and enable Paxman to take a monumental step towards their long-term goal of 'scalp cooling being offered to all chemotherapy patients worldwide, with Paxman as the natural choice'. The efficacy of scalp cooling treatment will be maximised through single-patient caps, promoting optimised cap fit and increasing treatment success. Single-patient caps will also promote enhanced infection-control, a factor of paramount importance due to chemotherapy-induced immune suppression, and particularly emphasised by the Coronavirus pandemic. Crucially, this project will also address the environmental impact associated with increased demand of this single-patient medical device. The focus on eco-design will promote the circular economy and minimise this products end-of-life impact.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: CANCER AND NEOPLASMS
Title: A novel therapeutic antibody to improve cancer treatment through the elimination of senescent cells
Funder: Innovate UK

Abstract: Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Miniaturisation Techniques for Dose Optimisation of Chemotherapeutic Agents (miniDOC)
Funder: Innovate UK

Abstract: As an Innovation Scholar, **Anand Pallipurath Radhakrishnan (APR)**, would swiftly transition from University College London (UCL) Electrochemical Innovations Lab (EIL) to work with the host company, **Vesynta Ltd.**, marking a new knowledge exchange partnership. **The miniDOC project**, led by UCL, will be partnered by Vesynta with additional input from multi-institutional academic partners and NHS clinicians, all **with a common goal of developing a point-of-care drug monitoring device with a pressing need in breast cancer therapy**. In pursuit of developing a dose optimising blood test device, APR will broaden his technical skills to advance smart engineering solutions **from a laboratory to the patient bedside in a healthcare setting**, satisfying a long-term career aspiration in the process. Rigorous device prototyping, scalable manufacturing techniques, _in vitro_ diagnostic regulatory requirements, robotic automation, and clinical trial design, are but a few skills APR would be equipped with through the miniDOC project. Additionally, Vesynta's core strengths, such as personalised medicine and monitoring, device manufacturing and prototyping, access to patient samples and a strong network of clinical and academic partners, will be exploited to significantly enhance APR's professional profile. **Career mobility is envisioned as APR will be considered for a Research and Development Technical Lead role within Vesynta** by the end of the secondment period. This further strengthens the implementation of a successful product development pipeline and truly supports the deployment of the device at the point-of-care. **Guidance and mentorship will be sought from UCL Institute of Healthcare Engineering** to ensure monitoring of the program objectives and to manage the associated risks. Simultaneously, this partnership shall leverage APR's skills in microfluidic engineering, advanced computational image analysis and biotechnology innovation, to solve challenges faced by Vesynta. During the secondment, **APR will facilitate cross-pollination of innovative ideas between UCL and Vesynta, seeking new avenues of research into bioanalytical sensing** furthering EIL's expertise in electrochemical analysis. Specific, measurable and achievable objectives have been drawn out to elicit APR's technical potential and to exploit Vesynta's core strengths, whilst accelerating the development of a platform that supports the practice of personalised medicine. **The successful delivery of the miniDOC project has the potential for a high impact on the treatment outcomes of cancer patients.** Through the adoption of safe and effective personalised drug monitoring practices with precision dosing aimed at adults with breast cancer, **the miniDOC project will make a direct impact on not only the healthcare sector but also on the economy**.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Fully humanised 3D vascular perfused model for breast cancer modelling and therapeutic screening
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Our technology has developed from two independently funded NC3Rs projects, uniting the Merry (developer) and Speirs (end user) groups. Merry has pioneered the development of self-assembling peptide hydrogels. These provide a fully tuneable matrix, devoid of any animal components, for disease modelling and therapeutic screening. Speirs is using a novel, synthetically vascularised, Organ-on-a-Chip screening platform, PerfusionPal, developed through NC3Rs CRACK IT by collaborator Vukasinovic and advanced though a current NC3Rs studentship to Speirs, to meet demands for physiologically closer in vitro platforms to model human tissues. The PerfusionPal model will be advanced by introduction of peptide hydrogels. Technological development and skills transfer will be driven by a postdoc. The hydrogel system will be incorporated into PerfusionPal and its effects tested experimentally, in perfused/unperfused conditions, against the current standard (Matrigel). We will identify optimal synthetic matrix components required to functionalise the 'naked' hydrogel, applying methods developed during Merry's current NC3Rs-funded project to generate gels with the preferred combination of physical and biochemical attributes to support the luminal A breast cancer model. The postdoc will visit Merry's lab to learn how to make hydrogels and apply this technology in Aberdeen. Cell viability assays will be performed, followed by live/dead Calcein AM/PI imaging. Further imaging will assess cell distribution throughout the hydrogel and identify changes in cell organisation due to the components selected to functionalise the hydrogel. A PerfusionPal platform, currently used by Speirs NC3Rs student in Leeds, will be relocated to Nottingham when the studentship ends (9/19). The system will be tested at both centres to ensure reproducibility. A free hands-on training workshop will introduce and promote uptake of the technology to the wider scientific community, with bursaries provided for ECRs.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Development of the chick embryo as a replacement for rodent models of tumour metastasis.
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Metastasis accounts for the majority of cancer deaths, yet it is one of the most poorly understood aspects of tumour progression. In order to reduce metastasis associated mortality it is crucial to understand how, when and where metastasis occurs. Metastatic dissemination is a complex process that involves several steps which can currently not be recreated in in vitro culture systems. Thus, in vivo models are used, of which murine models of cancer are the most common. Here, I aim to develop the chick embryo as a replacement for murine models of cancer. The chick embryo model is an excellent tool to study tumourigenesis and metastasis non-invasively as tumour cells can be easily engrafted onto its chorioallantoic membrane (CAM), an extraembryonic and highly vascularised membrane that is located directly beneath the eggshell and thus easily accessible. Within days, tumourigenesis and invasion occur and in the case of aggressive tumour samples, metastasising cells can disseminate to chick embryo's organs through haematogenous metastasis. Further advantages over murine models include its cost effectiveness, its simplicity and immunodeficiency, which allows the engraftment of any xenogeneic material. As the experiments will be terminated at E14, the proposed model is classified as non-protected under the Animals Scientific Procedures Act 1986 (amended 2012) and hence it is a valid animal replacement technique. Moreover, the chick embryo has the potential to be readily imaged in vivo using preclinical imaging and longitudinal high-throughput screening. Here I propose to establish its broader use as an exemplary in vivo model to investigate and intervene in tumour metastasis. This will be achieved by developing standard operating procedures (SOPs) for generating and detecting primary tumours as well as metastasis, and for the evaluation of therapeutics, thus encouraging a wide replacement of murine models for this purpose.


Research activity codes: 5.1 PHARMACEUTICALS;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Developing an in vitro repeat-dose test as a 3Rs approach to detect non-genotoxic carcinogens.
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Currently there are no validated in vitro tests to detect non-DNA reative (non-genotoxic)


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