NIHRDataInsights/HRCSData huggingface dataset:
Title: Cancer Research UK Formulation Unit for the pharmaceutical and biopharmaceutical evaluation of new anti-cancer drugs
Funder: Cancer Research UK

Abstract: The Unit is responsible for the preformulation, formulation, manufacture and testing of drugs for use in Cancer Research UK sponsored early clinical trials (Phase I and II) run by the Drug Development Office. Research involves initial chemical and physicochemical drug characterisation followed by development of a formulation for the intended route of administration, normally intravenous. Formulations range from simple aqueous solutions, to freeze dried products and capsules. Once a suitable clinical formulation is found it is extensively tested to determine appropriate manufacturing techniques and shelf-life. Product supplies will then be manufactured and despatched to the various clinical units involved in the trial. Continual product monitoring is then conducted to ensure clinical materials are of the highest possible quality. All research is conducted under a Quality Assurance system and manufacturing is performed to current Good Pharmaceutical Manufacturing Guidelines. Last updated 21/07/2010


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: CRUK/09/042: Gem-TIP: A multicentre phase II trial of salvage chemotherapy with Gem-TIP for relapsed germ cell cancer.
Funder: Cancer Research UK

Abstract: Approximately 85% of patients with newly diagnosed metastatic germ cell cancer will be cured when treated with an initial cisplatin containing regimen. The remaining 15% require salvage treatment which for the majority will comprise second line combination chemotherapy. The current UK standard in this scenario is TIP chemotherapy with 66% one year survival in an MRC trial. A more dose intense schedule of TIP with growth factor support achieved a two year progression free survival of 91%. Gemcitabine is an active drug in multi-relapsed germ cell cancer and has been shown to be manageable in combination with TIP with the addition of growth factor support in a phase I clinical trial. This study aims to evaluate the dose intensity of TIP which may be delivered in combination with Gemcitabine with growth factor support, relative to our previous study with TIP. In addition the activity of Gem-TIP combination chemotherapy will be assessed in patients at first relapse of metastatic germ cell cancer. Patients will be recruited at first relapse of metastatic germ cell cancer following cisplatin based chemotherapy. All patients will receive up to 4 cycles of full dose Gem-TIP with growth factor support with no dose reductions.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: CRUK/10/005: I-START: ISoToxic Accelerated Radiotherapy for Non-small cell lung cancer.
Funder: Cancer Research UK

Abstract: (1) Background: The commonest radical radiotherapy (RT) regimen for locally advanced non-small cell lung cancer (LA-NSCLC) in the UK is 50-55Gy in 15-20 fractions (3-4 weeks). Local control is poor (20-30%). Clinical data suggest there is a dose-response effect with RT, and increasing the prescribed dose may improve outcomes. This trial will assess the safety, activity and feasibility of an individualised, escalated-dose radiotherapy regimen, given in 20 equal fractions over four weeks, using 3-Dimensional Conformal Radiotherapy in inoperable patients. (2) Relevance: The standard of care for LA-NSCLC is combination chemo-radiation. Concurrent chemo-radiation is suitable for a proportion of patients with limited volume of tumour and able to tolerate chemotherapy. Patients not suitable for concurrent treatment due to co-morbid disease or tumour-related factors are suitable for radiotherapy and this can be optimised. There is a need to improve patient outcomes. It is probable that hypofractionated RT dose escalation may provide a similar magnitude of benefit to the concurrent schedules currently being used. (3) Specific aims: To establish the feasibility of this approach (proportion of patients completing planned treatment), the maximum tolerated dose to the oesophagus, the incidence and grade of other potential dose limiting toxicity, local control, disease-free survival and overall survival. (4) Outline plan (see flowchart): The trial is a single arm Phase I/II design. The dose for an individual patient will be prescribed as the maximum achievable dose within the range 58Gy-65Gy, by observing known dose constraints to the lungs, oesophagus, spinal cord and heart.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: CRUK/10/004: GeDDiS (Gemcitabine and Docetaxel versus Doxorubicin in Sarcoma)
Funder: Cancer Research UK

Abstract: Background: Doxorubicin is currently the first line chemotherapy of choice for locally advanced/metastatic soft tissue sarcoma. However, it is associated with only a 10-25% objective response rate, and benefits are short-lived with a progression free survival of 3-4 months. Ifosfamide, the current standard second line treatment, has been compared to doxorubin and has a higher response rate but greater toxicity. Phase II studies of gemcitabine and docetaxel in leiomyosarcoma specifically, and soft tissue sarcomas generally, have shown promising activity. There is now interest in using the combination in the locally advanced/metastatic setting. Aims: The proposed study is a prospective randomised controlled phase III trial which aims to determine whether the combination of gemcitabine and docetaxel is associated with an improved clinical outcome compared with single agent doxorubicin. Summary of proposed study: Patients will receive six cycles of assigned chemotherapy and will be followed for progression free and overall survival. Objective response rates will be evaluated. Both regimens will be comparatively assessed for toxicity and quality of life. A translational research component to the study will be developed using single nucleotide polymorphisms to investigate toxicity and response, and an analysis of pharmaco-economic impact will be performed.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Metastasis and Radiation
Funder: Cancer Research UK

Abstract: Despite surgery and/or radiation, many cancer patients, who appear to have localised disease, go on to develop distant metastases. My research group is interested in the mechanisms underlying the development of metastasis. We have used fluorescent microscopy to define the process of metastasis in the lung, finding adhesion of the tumour cells to the pulmonary blood vessels followed by spreading on the vasculature surface. Surviving cells give rise to early colonies formed within the blood vessels. Some outstanding questions which we would like to answer are: ◦What mechanisms do tumour cells use to arrest and survive at different metastatic organs? ◦How do tumor cells interact with the host vasculature during metastasis? ◦What are the mechanisms of metastasis to different organs, particularly the liver? ◦Why does irradiation of the lung or tumour affect metastasis?


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS
Title: Targeted Auger Electron Radiation Therapy for Cancer
Funder: Cancer Research UK

Abstract: The goal of the Experimental Radiation Therapeutics Group is the development of novel radiopharmaceuticals to image and/or treat cancer. Our four main research activities are: (1) The pre-clinical development of molecularly-targeted peptide-, antibody- and DNA-based radiotherapeutic agents, (2) Early phase clinical trials of novel radiotherapeutic agents, (3) The development of molecular imaging techniques (SPECT and PET) to diagnose and monitor cancer and (4) the investigation of the radiobiological effects of anticancer radiopharmaceuticals. This project focusses on Targeted Auger Electron Radiation Therapy for Cancer.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Wales Cancer Trials Network
Funder: Cancer Research UK

Abstract: The Wales Cancer Trials Network (WCTN) was set up in 1998 as a jointly funded collaboration between Cancer Research UK and the Welsh Assembly Government to benefit patients by providing support to cancer teams in Wales to take part in cancer research to improve treatments for cancer. The Network is an umbrella organisation for cancer clinical researchers in Wales. It aims to increase involvement and recruitment into trials by improving the infrastructure within the NHS for clinical research in cancer by sharing best practice, information and experience, to ensure that research is better integrated with cancer care across the NHS in Wales. The Network supports prospective trials of cancer treatments and other well-designed studies endorsed by government research councils, academic research groups and cancer charities. The WCTN aims to make research a more routine and acceptable part of high quality NHS care and to develop a research culture in the new cancer service in Wales. Investment, support and networking will improve the speed, quality and integration of cancer research and ultimately deliver benefits to patients more quickly. Since the WCTN was established, more than double the number of patients in Wales are now entering into cancer trials annually. The staff of the network are answerable to the WCTN Executive Committee. The WCTN reports through Wales Office of Research and Development (WORD) to the Welsh Assembly Government (WAG) and to Cancer Research UK (CR-UK). Further information about the WCTN can be found at http://www.wctn.org.uk/home.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: CANCER AND NEOPLASMS
Title: Cancer Research UK Centre for Cancer Therapeutics - Directorate
Funder: Cancer Research UK

Abstract: The Cancer Research UK Centre for Cancer Therapeutics is a unique academic drug discovery and development group. Its mission is to discover and develop novel and effective therapeutics for the treatment of cancer. Our aims are: * To identify and validate novel genes and pathways as targets for therapeutic intervention in cancer * To implement innovative technologies for drug discovery and development * By these means, to discover novel mechanism-based drugs and to develop these as rapidly as possible from the laboratory bench through to hypothesis-testing early clinical trials * To develop novel gene-directed enzyme prodrug therapies * As a result, to contribute to the improved treatment of human cancers


Research activity codes: 5.1 PHARMACEUTICALS;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);5.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Cancer Research UK Centre for Cancer Therapeutics - Synthetic Medicinal Chemistry 3
Funder: Cancer Research UK

Abstract: Our main focus is the discovery and development of small molecule inhibitors of various proteins implicated in cancer. These proteins are usually involved in cell signalling or control of DNA transcription and our initial chemical structures often (but not always) come from high throughput screening of chemical libraries. All of our work involves collaboration with molecular biologists, structural biologists, biochemists and pharmacologists both from within The Institute of Cancer Research and in other research centres and universities. Our input is mainly in synthetic and medicinal chemistry but can also include chemical insight into biological problems One current project involves targeting phosphatase enzymes which are involved in cell signalling via dephosphorylation of key proteins. Hits from high throughput screening have been generated and we hope to be able to apply structure-based drug design principles to the problem in the near future. In another area, we are investigating possible inhibitors of enzymes involved in the histone code which can control DNA replication. In collaboration with Prof. Bob Brown (Beatson Laboratory, Glasgow) we are synthesising and testing compounds which show activity in DNA mismatch repair-deficient tumours. We are also working on projects of a chemical biology nature, not designed to give a drug molecule. One example of this is a project in collaboration with Prof. Ernest Laue (Cambridge) to develop a new assay system for kinases using fluorescent tags on suitable molecular scaffolds. Finally, all the members of this team are organic chemists with (at the postdoctoral level) a background in synthetic chemistry or (at the PhD level) a desire to develop their synthetic skills in a multidisciplinary environment directed to real medical problems Consequently, we also develop new methods for the synthesis of drug-like molecules, for libraries of such molecules and for natural products which show useful biological activity.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);5.2 CELLULAR AND GENE THERAPIES
Health categories: CANCER AND NEOPLASMS
Title: Cancer Research UK Centre for Cancer Therapeutics - Target Discovery team
Funder: Cancer Research UK

Abstract: Chromosomal abnormalities are a hallmark of human cancer, reflecting the deleterious consequences of the gain or loss of genetic information. These abnormalities may be a consequence of tumour progression, mis-segregated chromosomes and aneuploidy. The fidelity of chromosome segregation is monitored by mitotic checkpoints that delay entry into mitosis until a functional centrosome is present. During this complex process, protein kinases play important roles in promoting or retarding transitions between different stages and checkpoints of the cell cycle. We aim to further understand mitotic control and use this information to identify and validate mitotic regulators as targets for cancer therapy. Currently one of our targets is the STK15 (Aurora2) gene, a mitotic kinase which has been found to be amplified in more than 50% of primary colorectal cancers and 12% of primary breast tumours as well as in breast, ovarian, colon, prostate, neuroblastoma and cervical cell lines. Thus, STK15 represents an attractive target for anticancer drug discovery. An additional field for identification and validation of genes involved in cancer is programmed cell death, also known as apoptosis. Apoptosis represents the defence mechanism of the cell with accumulated oncogenic mutations. Thus, defects in apoptotic signalling are thought to play an important role in the development of different types of cancers. It is not a surprise that the cell cycle and apoptosis are often deregulated in tumours. Therefore, they represent an attractive field for drug target discovery.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS
Title: Hit Discovery and Structural Design Team (CCT)
Funder: Cancer Research UK

Abstract: The Hit Discovery & Structural Design Team consists of the Structure-Based drug Design and the Analytical Technology and Screening Research groups. The team is responsible for the hit generation for our drug discovery projects using high-throughput and fragment screening approaches. We focus on a variety of cancer targets, including those involved in reversible protein phosphorylation, stress response, chromatin modification and targets involving specific protein-protein interactions. In addition, we support the design and improvement of the hits to potent and selective inhibitors with a range of assay and biophysical techniques as well as through iterative protein-ligand crystallography.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Cancer Research UK Centre for Cancer Therapeutics - Signal Transduction & Molecular Pharmacology
Funder: Cancer Research UK

Abstract: This Team has two major complementary roles: (1) To understand the molecular mechanism of action of drugs that affect, or are affected by, signal transduction pathways that regulate proliferation, cell cycle and survival in cancer cells; (2) To collaborate with other teams in the Centre and elsewhere to discover and develop innovative new drugs that act on novel molecular targets, defined by the genomics and molecular pathology of cancer. The Team is particularly involved in the development of inhibitors of the Hsp90 molecular chaperone, PI3 kinase and cyclin-dependent kinases. In addition we are interested in applying gene expression microarray and RNAi technology to understand the cellular pharmacology of molecular therapeutics and existing cancer drugs.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Computational biology and chemogenomics team
Funder: Cancer Research UK

Abstract: The last decade has witnessed an exponential growth of genomic data, and more recently structural and chemical data. A major challenge is to effectively utilize these diverse data in the development of new drugs. The team’s main aim is to empower translational research in cancer drug discovery by using computational techniques to bridge the gap between biological and chemical knowledge. We develop novel computational tools and approaches to effectively integrate biological, chemical and clinical data at large scale. These tools will be employed in the following areas: (1) Utilizing chemogenomics data to support decision-making in the drug discovery process, from target selection to lead identification. This should help identify opportunities and risks early on in the process thus helping streamline novel drug discovery; (2) Identifying patterns and rules in targets and networks which yield successful drugs, and applying these rules specifically in the complex field of cancer drug discovery, (3) Leveraging large scale structural biology and Structure Activity Relationship (SAR) data in determining target tractability and in aiding drug design, (4) Understanding rules governing ligand binding and target/ligand selectivity and using them predicatively in assessing target and compound development, (5) Utilizing published clinical outcome data to enhance the assessment and understanding of drug/target activities. These aims will be achieved through three major areas of research and development within the group: (A) Integrated chemogenomics workbench, canSAR, (B) Objective target assessment, (C) 3-D structural analysis


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Clinical Pharmacology and Clinical Trials Team (CCT)
Funder: Cancer Research UK

Abstract: The Clinical Pharmacology and Trials Team is responsible for the study of the preclinical and clinical pharmacology, and for the early clinical trials, of new anticancer agents developed in the Cancer Research UK Cancer Therapeutics Unit. Such investigations may include the study of mechanisms of action and resistance, toxicology, pharmacokinetics, early dose-finding studies and the development of pharmacodynamic biomarkers for the measurement of drug action in tumour and surrogate tissues. These may be molecular assays or functional imaging studies. The emphasis is increasingly on hypothesis-testing clinical trials of agents acting on new molecular targets including cell signalling, cell survival, the cell cycle control machinery, chromatin modulation and angiogenesis. The drug Metabolism and Pharmacokinetics (DMPK) Group (led by dr Florence Raynaud), within the Clinical Pharmacology and Trials Team, is a multidisciplinary group studying the pharmacokinetics of agents in clinical trials, such as 17AAG, 17DMAG and abiraterone. It is also leading the development of PI3K inhibitors. In addition, this group is evaluating the preclinical DMPK of novel chemicals under development in the Centre. Early assessment of DMPK allows liabilities to be identified and the early implementation of strategies to optimise drug-like properties. Aims * Clinical development of new discoveries within the Cancer Research UK Cancer Therapeutics Unit: o Develop novel agents for cancer treatment. o Discover, develop and apply new pharmacodynamic markers. o Develop non-invasive imaging techniques for evaluation of pharmacodynamic effects of anticancer agents in tumours. o Define the clinical context for novel targets and develop combination strategies for novel agents discovered at the ICR.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CANCER AND NEOPLASMS
Title: Centre for Cancer Therapeutics: Medicinal Chemistry Team One
Funder: Cancer Research UK

Abstract: Our research is focussed upon the design and synthesis of safe and effective drugs for the treatment of cancer by targeting specific proteins and pathways that are implicated in the disease. This work is conducted in close collaboration with biology, drug metabolism and clinical experts at ICR. The group works at all stages of the drug discovery process from the initial phases of target identification and hit discovery through to clinical candidate selection.Hit generation is achieved by high-throughput screening of in-house and external compound collections, fragment-based hit discovery, virtual screening and rational design. Lead optimisation of these hits is reliant upon the synthetic and medicinal chemistry skills in the team and continuous collaboration with biology, drug metabolism, computational chemistry and structural biology experts in ICR. Chemists work in multidisciplinary project teams and have an excellent opportunity to build expertise in the practice of a wide range of medicinal and synthetic chemistry skills. Current projects include the optimisation of Aurora kinase inhibitors (in collaboration with Chroma Therapeutics) and the discovery of inhibitors of the WNT pathway. In addition, we are actively exploring fragment-based hit discovery and developing expertise in in silico target design in ICR.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS