CORE A: Preclinical and Small Animal imaging
The Preclinical and Small Animal Imaging Core will help obtain the necessary package of data from in vitro, in vivo and human tumour specimens to warrant the development of drug development programmes or clinical studies exploiting new OIRO discoveries.
Clinically exploitable opportunities that arise from the proposed work of the OIRO MRC Unit will be successfully translated into biomarker studies, drug development opportunities or preclinical studies as appropriate. Therapeutic targets will be evaluated both in vitro and in vivo using the broad range of cell lines and murine models already available within OIRO. The animal facility embedded within OIRO is equipped with high quality imaging facilities including confocal microscopy, MRI, PET, SPECT, CT, ultrasound and a IVIS Spectrum for live fluorescence/luminescence imaging. Multiple radiotherapeutic systems including a customised MR-enabled SARRP irradiator, Gulmay X-ray generator and a LINAC capable of delivering FLASH radiotherapy are housed on site.
Work in this core will include testing novel compounds with different therapeutic strategies e.g., small molecules or protein therapeutics in regard to tumour control, normal tissue response, tumour physiology by specialist imaging modalities, irradiation of tumour and normal tissue by FLASH as well as conventional X-ray and SARRP irradiation. The core will provide many relevant techniques required to perform these in vivo experiments, including different administration routes (i.p, i.v, oral gavage), use of radiation platforms for tumour and normal tissues, tissue processing for IHC/IF or FACS and other ex vivo analysis.
The Preclinical and Small Animal Imaging Core has been instrumental in taking OIRO’s scientific findings from bench to clinic. One successful example is the repurposing of the anti-malarial drug atovaquone as a hypoxia-alleviating compound. Atovaquone was shown to reduce oxygen consumption in a high throughput screen and work in xenograft models subsequently showed that atovaquone reduced tumour hypoxia caused radiosensitisation in xenograft models. These findings were translated in a clinical trial confirming that it caused a marked reduction in tumour hypoxia in non-small cell lung cancer patients.
Novel therapeutic targets identified by the OIRO MRC Unit will be developed further with either commercial or academic collaborators as appropriate. The broader environment in Oxford is ideally suited for translational purposes. The Oxford University chemistry department has collaborated extensively with OIRO researchers to develop putative therapeutic compounds based on OIRO discoveries, and the neighbouring Target Discovery Institute has expertise in large-scale phenotypic screens and has previously collaborated with OIRO researchers such as D’Angiolella and Higgins to undertake successful CRISPR and compound screens, respectively.
OIRO researchers such as Giaccia, Higgins and Hammond have a track record of translating their laboratory findings into drug development programmes and ultimately into patient studies. The Oncology Clinical Trials Office (OCTO) and Early Phase Trials Unit in Oxford have substantial expertise in developing and delivery radiotherapy trials including studies involving drug combinations, novel functional imaging, and extensive tissue sample collection and analysis. During the next QQR cycle, OIRO will be involved in leading several clinical studies including the use of novel DDR inhibitors, hypoxia modifiers, and theragnostic agents.
