Overview of Research from the Centre for Cancer Research & Cell Biology, Queen s University Belfast. Kevin M. Prise
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1 Overview of Research from the Centre for Cancer Research & Cell Biology, Queen s University Belfast Kevin M. Prise
2 Centre for Cancer Research and Cell Biology (CCRCB) CCRCB Northern Ireland Clinical Cancer Centre
3 Cancer Research at CCRCB Belfast NHS Trust Belfast Experimental Cancer Medicine Centre Cancer Trials Centre Centre for Cancer Research & Cell Biology Industry Belfast Cancer Research-UK Centre University
4 Mission Statement Our mission is to improve patient care through the development of: Biomarkers for prognosis, prediction and markers of response Biologically determined targeted therapies
5 Focus Groups GU Thoracic GASTRO INTESTINAL BREAST HAEMATOLOGY RADIATION SCIENCES Enabling Technologies BIOINFORMATICS and IMAGING PATHOLOGY/TUMOUR BANK DRUG DISCOVERY CLINICAL TRIALS
6 Radiation Science at CCRCB Clinical Radiation Oncology Clinical physics Centre for Cancer Research and Novel Cell Biology fractionations Radiation Oncology R&D Radiation biology Experimental physics School of Medicine, Dentistry and Biomedical Sciences School of Mathematics and Physics School of Pharmacy School of Biological Sciences School of Chemistry Northern Ireland Cancer Centre Depts of Radiation Oncology and Radiotherapy Physics Northern Ireland Cancer Trials Centre
7 Radiation Sciences Research Themes 1 - Advanced Radiotherapies 2 - Drug-Radiation Actions Research Themes 3 - Radionuclide Therapy
8 Theme 1 Advanced Radiotherapy Clinical Trials In vivo Models Biomarkers Translational Radiation Biology CHiPP trial IMPORT Stereotactic Complexity indexes Data mining Advanced Radiotherapy Spatial and temporal effects Bystander signalling Normal tissue responses Radiotherapy Physics Experimental physics Microbeams Charged Particles Anti-protons Monochromatic photons
9 Clinical Research in Radiation Belfast External Beam Prostate PRO7 CHHiP Prostate Bladder scan study 1+2 MRI CT Fusion study Radiation Biomarker study EORTC Prostate cancer RT QoL study Radicals STAMPEDE Bone seeking Radionuclide Taxium Alpharadin phase External Beam other sites Spinal Cord Compression study (all cancer) Cabernet Study (Macular Degeneration) BC2001 (Bladder) PETCT (Lung) QUARTZ (Lung) IMPORT LOW (Breast) ACT II (Anal) PRIME (Uterus) SUPREMO (Breast) ART DECO (H&N) ARISTOTLE (Rectal) Clinical lead: Joe O Sullivan
10 Conventional Radiotherapy A few beams are directed to the target to give a uniform dose over a large area (which includes the tumour) A large volume is exposed to high radiation dose Conventional External Beam 3D Conformal Radiotherapy (3D CRT) Bladder Low dose volume rectum High dose volume Prostate tumour
11 Clinical linacs for radiotherapy For radiotherapy mostly high energy X rays (6 20MV) are used generated from a linac The treatment head rotates around the patient In the head of the linac a multileaf collimator consisting of interleaved tungsten leaves can be used to shape the beam
12 New biological models for advanced radiotherapy Test biological effectiveness of clinically relevant spatial and temporal radiation exposures Determine the impact of bystander signalling and underlying mechanisms Develop new in vivo models for testing clinically relevant protocols Develop new metrics for treatment planning of advanced radiotherapy from TCP/NTCP Kevin Prise / Stephen McMahon / Giuseppe Schettino / Joe O Sullivan / Alan Hounsell
13 Biomarker / Biodosimetry Studies For advanced radiotherapies suitable biomarkers need to be developed which can be used as surrogates for treatment efficacy Aims Undertake a clinical study is assessing a DNA damage markers as biodosimeter and biomarker in patients undergoing prostate radiotherapy and brachytherapy Develop studies with markers of normal tissue damage Darren Brady, Kevin Prise, Joe O Sullivan
14 Bladder Toxicity For advanced radiotherapy of the prostate the bladder is a limiting normal tissue Mechanisms of toxicity are poorly understood Aims: To investigate the cellular and molecular basis of radiation induced bladder dysfunction using targeted irradiation approaches To investigate the potential of novel urinary biomarkers to predict chronic bladder toxicity (BUSTin biomarker study being initiated) Lead: Karen McCloskey Rodent bladder ex vivo contraction assay Sham Day 0 20 Gy, Day 0 nerve stimulation 5 min 0.5 g
15 Advanced Models for Ion beams Developing and future radiation based therapies will utilise ion beams (Protons, carbon ions) Aims Optimise delivery on the basis of physical and biological mapping of the Bragg peak using experimental and clinically relevant beams Map lethal and non lethal damage mechanisms in cell and tissue models to develop new biophysical models Lead: Giuseppe Schettino
16 Theme 2 Radiation drug interactions Clinical Trials New agent development Breast & Ovarian Radiation drug interactions Prostate & Bladder GI Cancer Lung Nano materials Radiation biology Gold nanoparticles BH3 mimetics C-FLIP inhibitors PARP Inhibitors (+/- 5FU) Chemokine Signalling Radioresistance / stem cell models
17 Studies with gold nanoparticles Gold nanoparticles hold significant potential as novel radiosensitisers and contrast agents Aims Develop new biophysical models to predict their effectiveness Develop novel tagging strategies to target these at the tissue and subcellular levels Lead: Fred Currell
18 Studies in Glioma Optimise use of radiotherapy in glioma using new image guided preclinical models Probe mechanisms underpinning radiationinduced invasion in glioma and develop drug targeting strategies including nanotechnology approaches Develop appropriate biomarkers for relapse and second line interventions Lead: Tom Flannery
19 Molecular stratification in localised prostate cancer Key genetic events involved in the pathogenesis of prostate cancer induce or modulate the DNA damage response (e.g. PTEN, BRCA1/2) Optimal design and scheduling of DNA repair modulation of advanced radiotherapies will also be impacted by intercellular signalling Test role of beam modulation in key genetic models in vitro and in vivo Feed into CCRCB Translational Prostate Program Leads David Waugh, Kevin Prise and Richard Kennedy 19
20 Theme 3 Radionuclide therapy Clinical trials Translational radiation biology Radionuclide Therapy Dosimetry and modelling Novel Radionuclide combinations Bone seeking radionuclides for metastasis in resistant prostate cancer
21 Novel bone seeking therapeutics Clinical trials with bone seeking radionuclides have shown great promise in advanced prostate cancer trials Aims Develop new agents around innovative ionic liquid and phosphate chemistry Design optimal strategies of diagnostic/ therapeutic response to be tested in preclinical models Lead: Marie Migaud
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