NIHRDataInsights/HRCSData huggingface dataset:
Title: Enabling stratified medicine through cell and tissue reference standards for minimally invasive cancer testing
Funder: Innovate UK

Abstract: This project will deliver innovative products that drive the development of enhanced analytical systems to meet the changing needs of diagnosis and stratification of cancer patients. This will allow patients to benefit from recent advances in molecular pathology by delivering more reliable and earlier diagnosis, personalized therapies and disease monitoring to achieve improved outcomes. The project will develop, test and validate materials derived from cell lines that will be engineered to reflect the genetic modifications seen in different cancers. This approach will enable the project partners to produce new and highly innovative reference standards (including formalin fixed paraffin embedded cell blocks and genomic DNA) as well as methods and protocols that can be used in all laboratories to increase efficiency and sensitivity of diagnostic testing and enable standardized, controllable proficiency testing across all geographical locations.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: MOTI1001: Oncojan based drug candidate for the treatment of ovarian cancer
Funder: Innovate UK

Abstract: One in three of us will get cancer and increases in life expectancy indices will only exacerbate this statistic. Unfortunately, many cancer subtypes have very poor survival rates. Most chemotherapeutics have devastating side effects such as hair loss, nausea, weakened immunity and fatigue. BioMoti is developing an exciting technology platform based on Queen Mary, University of London research to improve the delivery of anti-cancer drugs to cancer cells and spare healthy tissues. Initial laboratory tests proved this new approach dramatically increases the efficacy of chemotherapy whilst significantly reducing associated side effects. This TSB Biomedical Catalyst project will investigate the feasibility of developing a lead candidate for the treatment of ovarian cancer based on the platform technology. Looking forward, the conceptual demonstration of the technology and widespread adoption would lead to substantial patient benefits in a number of cancer types.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: OptiLinked Antibody Drug Conjugates for Cancer Therapy
Funder: Innovate UK

Abstract: PhotoBiotics is a biotechnology company established from Imperial College London to develop antibody drug conjugates (ADCs) to treat cancer and other associated diseases. Its patented OptiLink platform enables high drug loading of small antibody fragments leading to enhanced formulation, tumour specificity, reduced side effects and high potency. In this TSB co-funded project, PhotoBiotics is exploring how the OptiLink platform can be used to target and reformulate an existing poorly soluble cancer chemotherapy drug - doxorubicin. The resulting drugs could be safer and easier to administer, with higher levels of potency due to their tumour specificity.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Proving the feasibility of using SMYD3 inhibitors as therapeutics for treatment of hepatocellular carcinoma and other cancers.
Funder: Innovate UK

Abstract: Our aim is to establish the feasibility of a new treatment for cancer that works by targeting the enzyme SMYD3. Recent academic research has shown that SMYD3 is not present in normal cells, but in many cancer cells it switches on the production of other proteins that help tumours grow and spread throughout the body. So this work suggests that a drug that inactivates SMYD3 will switch off these mechanisms, and have powerful anti-cancer properties, perhaps with few side-effects. This new mechanism would be very different than those of existing drugs, and of many other experimental treatments. This project will test this idea by identifying SMYD3-blocking compounds, and finding out whether they have the expected effects on tumour cells, and are safe to normal cells. If successful, this project will provide the starting-points for a larger programme to find a drug candidate that works in this way.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Feasibility assessment of a novel vaccine platform for the stratified therapeutic vaccine intervention in non-small cell lung cancer.
Funder: Innovate UK

Abstract: One in three of us will be affected by cancer during our lifetimes. Given the ever increasing burden of disease and an ageing population, the costs of providing optimal care in Britain alone will rise by a staggering 62% over the next decade. Current healthcare models and practices are unsustainable. Immune Targeting Systems Ltd is a London based Biotechnology Company developing innovative vaccines technologies against for mutating viruses (influenza and hepatitis-B) and is now extending the platform pipeline into oncology, initially in non-small cell lung cancer. This project is the first stage of this new investment through feasibility assessment of the use of an in vitro assay as a stratification tool for cancer vaccines peptide antigens: (1) to select tumour associated antigen derived long peptides for vaccine inclusion, and (2) to select patients suitable for vaccine intervention. Thereby providing a clear clinical development plan for a novel stratified therapeutic oncology vaccine.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: DEVELOPMENT FEASIBILITY OF A NOVEL SUPERIOR HER2-SPECIFIC TARGETED DRUG CONJUGATE FOR CANCER THERAPY
Funder: Innovate UK

Abstract: F-star is an oncology-focused biopharmaceutical company and is applying its Modular Antibody Technology to the development of a pipeline of bispecific antibody products. F-star's modular approach is based on introducing an antigen binding site into the Fc fragment of an antibody. The resulting Fcabs can be used to rapidly generate a bispecific from any antibody. The relatively long serum half-life and potential for improved tissue penetration of these Fcabs suggests that they will be particularly well suited to an antibody drug conjugate (ADC) approach. F-star has generated an Fcab which binds potently to Her2 and has demonstrated promising efficacy in mouse xenograft models. In this project F-star will conjugate a cytotoxin to its anti-Her2 Fcab and evaluate the resulting antibody drug conjugate alongside current standard of care treatments in mouse xenograft models.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: The use of High Content Phenotypic screening to guide the clinical management of cancer treatment.
Funder: Innovate UK

Abstract: Beating cancer requires a treatment that kills cancer cells but leaves normal tissue unharmed. While this seems simple enough it is actually very difficult because cancer cells look so much like normal cells when it comes to treating with anti-cancer drugs. The drugs that are available to treat cancer all aim to target cancer cells in preference to normal cells but how good they are at doing this will depend on how toxic they are to the cancer of that particular patient. If a particular cancer is very sensitive to a drug then it can be used at lower doses thus minimizing nasty side effects. Similarly if the cancer is very resistant to a drug then using it will only damage normal tissue and make the situation worse. The currently funded project aims to develop a clever diagnostic assay that will tell the clincians which of the available drugs will be most effective for each patient thus personalising the treatment of cancer and so helping those who are afflicted with this terrible condition.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Identifying deubiquitylating enzymes (DUBs) as targets for treating of platinum-resistant ovarian cancer
Funder: Innovate UK

Abstract: Novel therapies tailored for treatment of platinum-resistant ovarian cancer is an area of clear unmet need. Ovarian cancer is responsible for more deaths per year than any other cancer of the female reproductive system and developing drug resistance remains the main limitation of current chemotherapies. We propose an innovative approach to identifying novel drug targets for drug-resistant ovarian cancer that would exploit the very changes in the tumour that have led to the resistance. We propose to do this by screening all known human deubiquitylases (DUBs) – a novel, druggable class of enzymes – to identify innovative targets whose inhibition would selectively kill or re-sensitise drug-resistant ovarian tumours. The best validated targets will then enter the MISSION Therapeutics Ltd pipeline for further drug discovery efforts with a view to new, innovative and effective chemotherapies entering the clinic.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Feasibility study of TRANSPATH: novel software technology platforms for tissue biomarker quantitation for stratified medicine & oncology drug development
Funder: Innovate UK

Abstract: One in 3 of the UK population will develop cancer at some point in their lives. As a patient or a relative your major concern is to find a treatment that will be succesful in slowing down or curing the disease. Although there have been massive advances in our understanding of cancer in the last 20 years, we are still struggling to develop effective drugs with minimal side effects. We could vastly improve this by developing tests that will determine which is the right drug for the right patient. Currently some tissue based tests are available for patients but we are still held up by the fact that we are still using traditional subjective methods to report these tests that do not always have the sensitivity required. Pathology Diagnostics Ltd. is merging advances in computer imaging and other digital technologies with pathology to develop point of care computer applications that will be used alongside these assays to provide accurate quantitative tissue based testing in the clinic.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Assessment of the feasibility of developing an in vitro screen for epigenetic mutagens
Funder: Innovate UK

Abstract: The human genome is complex and well protected by an array of systems that sense damage, and initiate repair. When damage is overwhelming, cells are usually forced into suicide to minimise the generation of viable mutant cells that might develop into tumours. Direct DNA damage is not the only threat to the genome. Tissues such as liver, kidney, muscle etc are different because they express different subsets of genes from the same human genome. Active genes are more loosely packaged than inactive genes; inactive genes are more likely to have modified DNA bases compared to active genes. This regulation, above the DNA sequence, defines the science of epigenetics. The distinctive and lifethreatening cells found in tumours also have distintive epigenetic signatures, and in this project it is aimed to determine whether it is possible to detect epicarcinogens in a simple lab test that can detect changes in these signatures of gene expression.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Clinical version of the Physiomics Virtual Tumour
Funder: Innovate UK

Abstract: Personalised medicine can be broken down into three key questions: which drugs do we give to a particular patient, how much and when? While many companies are seeking to address the first question, dosing and scheduling issues are poorly understood. Attrition rates in oncology remain high, part of the problem being that dosing and scheduling regimens are not optimised at the clinical trial stage. Physiomics has already developed the Virtual Tumour technology, which is used by our customers to optimise the dosing and scheduling of cancer drug candidates. However, the current version of the technology is only applicable to pre-clinical experiments. The company is now proposing a project to develop a clinical version of the Virtual Tumour. This would initially improve the success rate of cancer drugs proceeding through clinical trials. In the long run, if such a technology could be applied directly to patients, it would lead to real improvements in overall survival rates.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Video Rate Blood Flow Imaging for Reconstructive Plastic Surgery
Funder: Innovate UK

Abstract: Reconstructive plastic surgery is in the front line for the removal of cancerous tumours of the breast, head, neck and other sites. Reconstructions following tumour removal usually require the replacement of removed tissue with tissue (i.e. skin, fat, muscle, bone) from other body sites to complete the procedure. The transferred tissues rely on an adequate blood supply to avoid complete or partial failure. The Laser Speckle Imaging technique (LSI) is a new and fast way of seeing blood flow in the skin and other tissues enabling surgeons to optimise tissue blood flow during surgery. The new LSI technique scans areas of up to 15cm x 20cm at video frame rates; larger and faster than other techniques. The purpose of this proposal is to examine the feasibility of applying the new technology for reconstructive plastic surgery. This will benefit patients by avoiding the trauma of a failing reconstruction requiring additional surgery and it will therefore reduce NHS costs.


Research activity codes: 6.4 SURGERY;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: SAR studies to validate novel Fatty Acid Synthase (FASN) inhibitors as anti-cancer therapeutics
Funder: Innovate UK

Abstract: The enzyme Fatty Acid Synthase (FASN) has been shown to be a key therapeutic target in cancer. Most normal cells acquire fatty acids from diet, so do not require or express FASN. By contrast, many types of cancer cell express high levels of FASN, and this expression is associated with poor patient prognosis. Sareum has discovered a novel series of inhibitors of FASN that are able to prevent cancer cell proliferation. The aim of this feasibility study is to investigate whether chemical modification of these inhibitors can improve their potency and stability, and thus warrant the investment in a full lead optimisation programme to develop candidate molecules for clinical trials in patients


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: The Regulation of DNA Replication Initiation
Funder: Worldwide Cancer Research

Abstract: Healthy cells grow and divide in a highly organised manner, for example to replace dead skin cells or to heal a wound. Cancer occurs when something goes wrong and the cells become able to grow and divide in an uncontrolled manner, forming a tumour. The division of cells, to produce two new cells, involves a series of steps known as the cell cycle. Before a cell divides, it firstly has to copy its entire DNA (the genetic material) and then give one complete copy to each of the new cells. Errors in the copying of the DNA are one of the causes of cancer. To help reduce errors the cells only allow DNA to be copied at a particular time in the cell cycle. Many of the molecules involved in this copying process have been identified but the way in which they are regulated and their exact role is still unclear. The copying process starts when a group of molecules come together, known as the Pre-Initiation Complex and this is the focus of this research. In order to study this complex both human cells and yeast are being used. Yeast are very similar to human cells, but they are less complicated and easier to work with, and they provide an opportunity to understand biological problems before they can be tested directly in humans. Also being investigated is how the Pre-Initiation Complex assembles and disassembles at defined time points during the cell cycle. Many molecules in the Pre-Initiation Complex become damaged or altered in cancer but how this contributes to the development of cancer is yet unknown. In addition, its believed that several key components of the Pre-Initiation Complex have not yet been found in human cells and it is his aim to find these molecules and analyse their possible role in the onset of cancer.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Functions of mutant p53 in cancer cell invasion
Funder: Worldwide Cancer Research

Abstract: "One of the key clinical problems in the treatment of cancer is the dissemination of the disease to distant organs, known as metastasis. Patients presenting with metastatic disease generally have a much poorer outcome and current treatments are not effective in the cure of metastatic disease. Complex biology underlies how tumours spread and reflects changes in both the cancer cells and their environment. However, understanding these pathways is critically important for the development of new approaches to treat invasive disease. Mutations in the p53 tumour suppressor gene are found in most cancers, frequently leading to the expression of a mutant p53 protein. These mutant forms of p53 are not only disabled in the normal activities of p53 (which function to restrain malignant progression), but also result in the acquisition of novel functions that helps to promote invasion and metastasis. Since these mutant proteins are expressed only in cancer cells, they make an attractive target for potential therapeutic intervention. This project aims to understand more fully how these mutant p53s function, with the aim of indentifying novel approaches for cancer treatment. The focus of the studies will be to expand our previous work demonstrating an ability of mutant p53 to promote signalling from cell surface receptors that are known to have a well-established role in cancer development. The identification of further signalling pathways controlled by mutant p53 may help to guide treatment protocols of cancers that express these proteins. We will also investigate more fully the role of other p53 family members in the response to mutant p53, with emphasis on the role of TAp63, a protein recently found to play an important role in the regulation of metastatic behaviour."


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Role of hMOB2/HCCA2 (human carcinoma-associated 2 protein) in cellular transformation of human cells
Funder: Worldwide Cancer Research

Abstract: "The novel mammalian Hippo tumour suppressor pathway functions with NDR/LATS kinases as central players. NDR/LATS kinases are regulated by binding to hMOB1, while hMOB2 only binds to NDR1/2 kinases. hMOB2 competes with hMOB1 for binding to NDR1/2, thereby negatively regulating at least two cancer-related processes, namely centrosome and apoptosis biology. Since centrosome abnormalities can result in genomic instability, deregulated hMOB2 expression might lead to at least two hallmarks of cancer, evasion of apoptosis and genome instability. Currently, detailed studies addressing the involvement of hMOB2 in cellular transformation processes are lacking. Therefore, we propose to address the following objectives: (1) Define the role of overexpression/loss of hMOB2 in cellular transformation Studies of untransformed human cells expressing shRNAs/cDNAs in a Tet-on manner will define how far deregulated expression of hMOB2 causes loss of contact inhibition, foci formation, increased growth in soft agar, and xenograft models. (2) Decipher cancer-related processes controlled by hMOB2 The roles of hMOB2 in apoptosis and centrosome biology will be tested together with possible changes in cell cycle progression and EMT. This will reveal through which cell biological processes human cells can be transformed by altered hMOB2 expression. (3) Address the role of hMOB2/NDR interactions in cellular transformation By using already existing hMOB2 mutants, we will address the difference between hMOB2/NDR1 and hMOB2/NDR2 complexes, as well as complete loss of hMOB2 binding to NDR. (4) Identify and characterise novel hMOB2 binding partners In collaboration with dr Pasterkamp, we will screen human cell lysates for novel hMOB2 binding partners. The aim is to unveil how hMOB2 regulates cancer-related processes dependent and independent of NDR kinases. (5) hMOB2 expression in the cancer predisposition Beckwith-Wiedemann Syndrome In collaboration with dr O’Driscoll, we will characterise BWS derived cell lines to define whether altered hMOB2 expression is associated with BWS."


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Roles of Rho/PKN3 and Cdc42/ACK1 in prostate cancer invasion
Funder: Worldwide Cancer Research

Abstract: "Prostate cancer is the second leading cause of cancer mortality in men, and death is usually a consequence of metastasis. The Met tyrosine kinase receptor is activated by HGF and contributes to cancer progression by promoting invasion and metastasis. Met deregulation correlates with poor prognosis and aggressiveness in many cancers, including prostate cancer. Rho GTPases and their effectors are involved in cell adhesion, migration and extracellular matrix degradation and play a central role in Met-induced migration and invasion. However it is still not well known how Rho GTPase pathways orchestrate the invasive phenotype downstream of Met. The aim of our project is to determine how Rho GTPases and their effectors contribute to Met-induced prostate cancer cell invasion. To this purpose we have screened a siRNA library targeting two hundred genes, including all Rho GTPases, their regulators and effectors, using a 3D invasive morphology-based assay in response to HGF stimulation. We have identified as hits Cdc42 and three related GTPases (RhoJ, RhoQ and RhoV), and their potential downstream effector kinase ACK1, as well as RhoB and its putative effector kinase PKN3. We will investigate how Cdc42-related GTPases and RhoB signal downstream of Met, by assessing ACK1 and PKN3 activation and subcellular localisation in response to HGF stimulation. We will determine which Rho-related and Cdc42-related GTPases regulate and interact with PKN3 and ACK1 respectively. We will also investigate the role of Cdc42/ACK1 and Rho/PKN3 in Met signalling and trafficking. We will interfere with Cdc42/ACK1 and Rho/PKN3 signalling pathways and assess their effects on invasion in vitro and on prostate cancer cell growth and metastasis in vivo. Our work should identify new signalling pathways involved in Met-driven invasion in prostate cancer, in particular the kinases ACK1 and PKN3, which could be new targets to develop inhibitors preventing metastasis."


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