NIHRDataInsights/HRCSData huggingface dataset:
Title: Genomic and expression profiling of recurrent well differentiated and dedifferentiated liposarcomas
Funder: Sarcoma UK

Abstract: Background: Liposarcomas (LPS) are a heterogeneous group of tumours that show features of adipocyte differentiation. Well-differentiated (WD) and de-differentiated (DD) LPS together comprise the most frequent soft tissue sarcoma in adults. Recurrences appear more undifferentiated, frequently in the retroperitoneum where mortality approaches 100%. Aim: To comprehensively define the genomes and gene expression profiles of WDPLS and DDLPS in order to identify quantitative and qualitative changes associated with recurrence and a more undifferentiated phenotype. Plan of Investigation: Well-annotated snap frozen LPS samples collected over many years from the Royal Marsden Hospital will be used. We have carefully selected cases with chemo-naive retroperitoneal WD/DDLPS of similar size that were fully resected according to margins and had similar stage and grade of disease. The total number of samples, including paired normal tissues, for in-house exomic DNA sequencing and copy number analysis is 25. Sequence changes will be confirmed by Sanger sequencing and copy number changes by quantitative PCR or interphase fluorescence in situ hybridisation analyses, extended to a further sample set. Gene expression profiling will also be performed on the primary tumour samples set to identify genes differentially expressed between primary tumours and recurrences as well as those associated with a more undifferentiated phenotype. In addition, nucleic acids from available LPS cell lines that we have recently been able to differentiate, will be analysed. Changes may mirror those in the primary tumours and be useful models for subsequent experimental analyses. Expected outcome: This study will identify key changes in the genes of WDLPS and DDLPS. Those associated with tumour differentiation and recurrence will then be incorporated into ongoing funded investigations that may have implications for predicting, preventing or treating recurrent LPS.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Assessing the potential of circulating tumour DNA as a new biomarker for low grade bone and soft tissue neoplasms
Funder: Sarcoma UK

Abstract: It is now well established that at least certain solid tumours release significant quantities of DNA into circulation. This cell-free circulating tumour DNA (ctDNA) has a range of potential clinical uses from patient stratification for treatment through to monitoring response to therapies. Recent genetic studies have described a range of common genetic aberrations in low grade sarcoma/neoplasms which are already being established as specific biomarkers in tissue. We propose a pilot study to investigate ctDNA levels before and after treatment in 7 bone and soft tissue tumour subtypes (benign, intermediate and low grade neoplasms): Low grade chondrosarcoma, chondroblastoma, desmoid fibromatosis, fibromyxoid sarcoma, fibrous dysplasia, giant cell tumour of bone, and solitary fibrous tumours. The spectrum of tumours has been selected on the basis of them harbouring diagnostic genetic alterations in the vast majority of cases, that is, point mutations or rearrangements. We will develop digital PCR assays to the most common mutations. We will then select approximately 10-20 of each tumour type. We will assess all for these hotspot mutations in tissue then test the ability to detect the same mutations in circulation both before and after treatment. If successful, this would be the basis for the development of larger studies testing the utility of ctDNA quantification in the management of patients with this set of low grade neoplasms of connective tissue origin.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: The International Sarcoma Kindred Study: a global multi-site prospective cancer genetics study
Funder: Sarcoma UK

Abstract: Sarcomas are uncommon cancers that disproportionately affect young people, with a high mortality and significant lifelong morbidity despite intensive multi-modality treatment. Identification of individuals at high risk of developing sarcomas may lead to earlier detection and more effective treatment of these tumours. The recent study of somatic genetics in sarcomas has contributed greatly to our understanding of the genetic aetiology of sarcomas. However, inherited genetic risk factors are also important in sarcoma, impacting upon likelihood of second cancers, reproductive decision-making in young patients, and estimating familial risk for family members of sarcoma patients. Studies of familial aspects of sarcomas have already made fundamental contributions to cancer biology, in particular the roles of the retinoblastoma and p53 tumour suppressor genes. Moreover, recent developments in high-throughput genomic sequencing platforms have radically transformed the probabilities of identifying novel cancer genes from small numbers of human samples. In the clinic, familial sarcoma studies have so far been limited in that much work has been done in children, such that the 90% of sarcomas that arise in adults have not been represented. Thus, the International Sarcoma Kindred Study (ISKS), has been initiated in order to identify, validate and quantitate genetic risk in patients with adult-onset sarcoma. It is the first study of it’s kind and aims to recruit 3000 patients and their families.This an international initiative, with nine major international sarcoma centres in USA, Europe and Asia to ensure genetic diversity. This is an important and unique opportunity for the UK, not least for sarcoma patients and their families, giving them the opportunity to take part in , and potentially directly benefit from, this first-of-its-kind-in-sarcoma study.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Acropolis (Advanced Collaborative Research for Oncology Platform for Improved Outcomes, Learnings, Insight and Science)
Funder: Innovate UK

Abstract: Growing healthcare costs and poor patient outcomes is driving increased interest in collaboration to support stratified medicines as a means to deliver targeted, safe and cost effective treatments. Research into stratified medicines is severely curtailed by poor access to high quality patient data and the deluge in associated genetic, molecular and image information. The innovative Acropolis platform will provide the essential informatics infrastructure to support secure stratified medicine research and collaboration, including data handling, storage, retrieval and analysis services that will acquire, pseudonymise and integrate data from a wide variety of diverse sources. Acropolis has a strong consortium led by R&D data management firm IDBS, supported by hosting firm Quantix and leading cancer institutes at Manchester and King’s Health Partners. The Acropolis consortium has all the components to successfully support translational research activities and will ultimately help deliver improved treatment of cancer and other diseases across global healthcare systems


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Development of a fully integrated service for sequencing-based tumour profiling including data interpretation and commercialisation of assay panel kit products
Funder: Innovate UK

Abstract: The aim of this project is to develop a tumour profiling assay based on targeted multiplexed enrichment and next generation sequencing (NGS) of clinically informative genes and variants. Oxford Gene Technology (OGT) will work closely with its partners in Birmingham and Southampton, and the CR-UK Technology hubs to build the assay into an innovative, integrated workflow, from sample submission to interpretation of the patient tumour profile. As a final step, the data will be transferred into an automated prescription management system, developed by CIS Oncology, which will enable the output of the profiling to be closely coupled to drug prescription, ensuring accuracy and consistency of care and delivering significant cost savings to the NHS. OGT will investigate the potential, not just to commercialise the assay panel, but also to offer a centralised, high-throughput, validated service run from OGT's accredited laboratories.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: EktoTherix: Initial clinical evaluation of a regenerative tissue scaffold for repair of surgical excision wounds
Funder: Innovate UK

Abstract: Neotherix (York UK) has developed the EktoTherix™ bioresorbable scaffold material that assists patient tissue repair and regeneration, with an initial target clinical application of non-melanoma skin cancers (NMSC) with further indications to follow. A patch of the material is used following excision of the basal or squamous carcinoma by the clinician, and this rapidly allows the wound space to be filled with (and then covered by) the patients’ own skin cells. This TSB funded project will continue the development of the product towards full commercialisation, with further development of the product registration package leading to a clinical evaluation involving a small number of patients. The team will also complete a health economics evaluation prior to launching the product within the UK and EU market in 2013/2014. The estimated global market for this product for NMSC alone is £867m pa.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES;5.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: 'First-In-Man' directed pre-clinical development of an anti-cancer agent - CYC065
Funder: Innovate UK

Abstract: Cyclacel has developed a novel clinical candidate NCE affecting previously unexplored pathways for treatment of acute leukaemia. The compound has a strong rationale for use as a stratified medicine for adult, infant and paediatric indications which have a high unmet medical need. The drug development project encompasses preclinical validation of marker assays for clinical stratification of patients, 'First-In-Man' (FIM)-directed preclinical development, clinical formulation and manufacture of the compound for Phase 1 testing, and testing of combinations with approved and investigational therapeutic agents to facilitate clinical development of the clinical candidate in the target diseases. Success will attract further investment in a UK and EU based development programme, securing additional jobs and will provide access to a new investigational medicine for both adult and infant patients with poor prognosis diseases.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Development of an Investigational New Drug for the treatment of pancreatic cancer
Funder: Innovate UK

Abstract: There is a continuing need for new and more effective medicines to treat cancer patients. Despite a steady increase in the number of clinical treatment options available to patients, the number of people being diagnosed with cancer is growing. Sentinel Oncology is a company dedicated to the design and development of new and innovative approaches for the treatment of cancer. The objective of this project is to identify a new drug suitable for the treatment of pancreatic cancer, a disease with very few, if any suitable treatments currently available and for which the prognosis for patients is extemely poor. The successful completion of this project will allow clinicians to develop clinical trials which will be designed to safely enhance the anti-cancer effects of current standards of care for pancreatic cancer.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Novel drug candidates for the treatment of castrate resistant prostate cancer
Funder: Innovate UK

Abstract: Prostate cancer is the second leading cause of mortality among men. Initial treatments focus on reducing the levels of circulating male hormones in the body which the cancer requires for growth. Overtime however, in 10-20% of cases, the cancer cells circumvent this treatment and develop into ‘castration-resistant’ prostate cancer (CRPC). This is the lethal form of the disease. CellCentric have identified an enzyme that regulates the cellular processes that lead to the development of this lethal form of the disease. It is proposed to identify and optimise an inhibitor of this enzyme as a potential new drug for the treatment of CRPC. On-going research at CellCentric has identified prototype inhibitors of the enzyme. The research proposal aims to optimise these inhibitors so that they can be assessed for anti-tumour activity in models of CRPC. If these ‘proof of concept’ studies are successful, a candidate compound will be nominated for further evaluation in human clinical trials.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Antibody Directed Phototherapy for Oesophageal Adenocarcinoma
Funder: Innovate UK

Abstract: Oesophageal Cancer is rapidly rising and is the 4th largest cancer killer in men. This project supports combining PhotoBiotics' proprietary OptiLink technology and its own drugs with experts from Imperial College and University College London National Medical Laser Centre to develop a novel antibody-directed phototherapy (ADP) drug to treat cancer. These drugs have few side effects and tumours cannot develop drug resistance to them. We have identified a clinically-validated target and have preliminary data to show that we can tackle this for Oesophageal Cancer. Photobiotics will oversee the manufacture and testing of the drug, Imperial College will help to generate functional data and UCL will treat tumours using their established models. If successful, thus funding will lead to major interest from the pharmaceutical industry to take this into clinical trials.


Research activity codes: 5.1 PHARMACEUTICALS;5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: 'First-In-Human' directed pre-clinical development of anti-cancer agent CYC140
Funder: Innovate UK

Abstract: Cyclacel has developed a clinical candidate NCE with characteristics enabling the targeting of a previously unexploited mechanism for treatment of oesophageal cancer (OEC), an orphan disease with a high unmet need. This potent and selective PLK1 kinase inhibitor has a strong preclinical rationale for use as a stratified medicine for OEC and other solid tumour indications having particular driver mutations. The drug development project encompasses preclinical validation of marker assays for clinical stratification of patients, 'First-In-Human' (FIH)-directed safety studies, clinical formulation and manufacture for Phase 1 testing, and testing of the compound in combination with approved and investigational therapeutic agents in models of the target diseases. Success will attract further investment in a UK and EU based development program, securing additional jobs and will provide access to a new investigational medicine for solid tumour patients with poor prognosis diseases.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Clinical Development of an Adoptive T cell Therapy for Triple Negative Breast Cancer
Funder: Innovate UK

Abstract: Adaptimmune has developed the adoptive transfer of T cells genetically engineered to express optimised affinity T cell Receptors (TCR) that target cancer peptide antigens. This approach generates potent anti-tumour immunity. This disruptive therapy has the potential to treat late stage diseases, such as Triple Negative Breast Cancer, for which there is a great unmet need and is not ammenable to targeted biological therapies. Such targeted T cell therapies represent a significant advance over traditional chemotherapy because they selectively attack the cancer and not the rest of the body offering significant increase in the patient standard of life. This project is for the development of a new TCR gene modified T cell therapy suitable for use in Triple negative Breast cancer and will and evaluate safety and efficacy to assess the potential of this therapy in a disease with a great unmet need.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES;5.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Clinical trial of a molecular imaging camera and laparoscope for prostate cancer surgery
Funder: Innovate UK

Abstract: Forty thousand patients are diagnosed with prostate cancer in the UK every year, and eleven thousand succumb to the disease. Early detection followed by surgery remains the most effective strategy to combat prostate cancer, yet nearly 1 in 4 patients with localized prostate cancer will see their cancer recur after surgery. Prostate cancer recurs after surgery primarily due to incomplete excision of the cancer. Surgeons are unable to completely remove the cancerous tissue because the naked eye cannot detect small cancer deposits. Further, sparing the nerves responsible for erectile function and urinary continence is a high priority. Consequently, there is a tremendous medical need for more sensitive tools to detect cancer during surgery. Lightpoint Medical is developing a molecular imaging camera and laparoscope to detect cancer in real-time during surgery, and thereby reduce the chance of cancer recurring. The technology is based on Cerenkov Luminescence Imaging (CLI), a ground-breaking imaging modality that can perform optical imaging of Positron Emission Tomography (PET) imaging agents. In this project we propose to conduct a pilot clinical trial for the CLI camera and laparoscope in prostate cancer surgery. The trial results will be used to assess the performance of the devices compared to gold-standard pathology, and to develop the next iteration of the products. Additionally, the UCL Centre for Medical Image Computing will research and develop an improved image processing module for the Lightpoint device.


Research activity codes: 6.4 SURGERY;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Stratification of Pulmonary Nodules in Incidental Findings and Lung Cancer Screening
Funder: Innovate UK

Abstract: Lung cancer is one of the most common cancers with the highest mortality rate both in the UK and Worldwide. In 2010, some 42,026 new cases were diagnosed in the UK and 34,859 lung cancer deaths recorded. In 2008, 1.6 million new lung cancer cases and 1.4 million deaths were recorded worldwide. Against this background, this project addresses a hugely challenging and unmet need in stratifying patients with Pulmonary Nodules (PNs), small masses in the lung, in Chest Computed Tomography (CT) scans. Such findings might typically occur in one of two situations: as incidental findings on scans unrelated to lung cancer, e.g. investigations for pulmonary embolism, or in lung cancer screening. In either situation, the problem is the same: nodules are very common in Chest CT and so either require further investigation, if sufficiently suspicious, otherwise follow-up imaging after 6, 12 and 18 months. However, most nodule are not cancers. Therefore, this project will develop new image-based stratification techniques for patients with Chest CT nodules. The project has two broad objectives. First, to develop new image processing technologies to make it much more efficient to read multiple Chest studies. Second, develop new image processing techniques coupled with new protocols where necessary to radically improve both the sensitivity and especially specificity of imaging of the lung.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Phase-insensitive Ultrasonic Computed Tomography (piUCT) for the diagnosis of breast disease
Funder: Innovate UK

Abstract: Annually, 49,500 UK women are diagnosed with breast cancer. However, 92,000 unnecessary biopsies are performed as only about 30% of suspicious lesions are found to be malignant. As each suspicious lesion must be confirmed by biopsy, better diagnosis would avoid unnecessary biopsy procedures, improve care and reduce cost to the NHS. The gold standard of triple assessment (clinical examination, X-ray mammography and biopsy) can be successful in women over 45 years of age. However, it can also miss up to 10 % of cancers in women under 35. A more sensitive and specific diagnostic method for younger women is needed. This is growing in importance as the number of women under 50 diagnosed with breast cancer is increasing and now stands at 1 in 5. There is also a need to monitor the progress of patients undergoing chemotherapy, which requires multiple scans. For this, X-ray mammography cannot be used as repetitive exposure can cause cancer. An alternative scanning tool is ultrasound imaging. We have developed a completely new kind of ultrasound detector that works by detecting small amounts of heat generated through absorption of ultrasound waves. We have demonstrated the potential of the new detector to generate images of improved quality, relative to conventional devices. This is an example of innovation in science and engineering opening up pathways for new clinical capabilities. The detector will be targetted at 3D whole breast scanning. We will improve current detection technology and develop a whole-breast ultrasound demonstrator system and, in a small clinical trial, we will test its ability detect lesions in women known to be suffering from breast cancer.


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: Pilot clinical study of an intra-operative molecular imaging fibrescope for breast cancer surgery
Funder: Innovate UK

Abstract: Nearly 1 in 4 breast cancer patients in the UK will see their cancer return after surgery. The consequences include repeat operations, delayed adjuvant treatment, increased likelihood of distant recurrence, poorer cosmetic outcomes, emotional distress, and enormous financial cost to the NHS. Breast cancer recurs after surgery primarily due to incomplete excision of the tumour or inadequate clearance of the surgical margins. Surgeons are unable to completely remove the cancerous tissue because the only tools they have to detect cancer during surgery are visual and tactile assessment. Consequently, there is a tremendous medical need for improved tools to detect cancer during surgery. Lightpoint Medical is developing a molecular imaging fiberscope to detect cancer in real time during surgery, and thereby tailoring the surgery to the individual patient's disease. The technology is based on Cerenkov Luminescence Imaging (CLI), a ground-breaking imaging modality that can perform optical imaging of Positron Emission Tomography (PET) imaging agents. Initial market research indicates a high demand for the technology among breast cancer surgeons in the UK and US. In this project Lightpoint and Guy’s Hospital will undertake a pilot clinical trial of the CLI fiberscope in breast-conserving surgery in order to assess the device's diagnostic performance. The results will be used to de-risk the technology before embarking on large-scale, pivotal clinical trials and to collect surgeon-user feedback on the device usability and performance.


Research activity codes: 6.4 SURGERY;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS