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Clinically relevant tumour models to identify novel approaches for the treatment of rectal cancer


Project Description

Oxford is part of a Cancer Research UK funded consortium called ACRCelerate (https://bit.ly/2YH1Pou; led by the Beatson Institute in Glasgow) which has been funded to expedite the pre-clinical evaluation of novel therapeutic approaches in colorectal cancer. Rectal cancer differs from proximal disease in terms of somatic mutation spectrum, clinical behaviour and response to treatment, but remains a difficult disease to model in mice.

As part of the ACRCelerate programme, novel models of rectal cancer have been established that will be used to test new drugs in combination with targeted radiotherapy. Firstly, using a mouse colonoscope guided needle injection, localised rectal villinCreER Apcfl/fl tumours can be established via a submucosal injection of tamoxifen. Secondly, rectal tumours can be induced by dextran sulfate sodium (DSS) treatment in a villinCreER KrasG12D/+ p53fl/fl Rosa26N1ICD/+ genetic background, to direct tumour specifically to the rectum. Thirdly, we can use submucosal injection of syngeneic tumour organoids. In Oxford, the small animal radiation research platform (SARRP) is well established and this targeted preclinical irradiator, linked to a high specification MRI scanner, enables clinical quality targeted irradiation to be delivered to the tumour, while sparing normal tissues. In this DPhil project, the student will utilise these refined models of distal colon/rectal disease to explore tumour and normal tissue responses to novel agents, including those targeting the immune system, the DNA damage response, and the tumour microenvironment.

The project is funded by Cancer Research UK for 4 years and includes a stipend of £19,000 per year in addition to running expenses and fees (at UK/EU level). The successful candidate will have some previous experience of in vivo biology, and preferably be a current or recent holder of a UK Home Office PIL.

How good is research at University of Oxford in Clinical Medicine?

FTE Category A staff submitted: 238.51

Research output data provided by the Research Excellence Framework (REF)

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