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The Department of Oncology offers to science graduates and clinical research fellows the opportunity to undertake doctoral research leading to a Doctor of Philosophy (PhD) degree via two courses 1) DPhil in Oncology or 2) DPhil in Radiation Oncology. Applicants may choose from a list of advertised projects or may apply for a different research project agreed with the Principal Investigator.

The DPhil in Oncology programme of study offers up to four-years of study with subject areas covering the entire spectrum of oncology.

The DPhil in Radiation Oncology (1+3) is a four-year combined MSc and DPhil programme, with subject areas for the three-year DPhil portion covering the spectrum of oncology relevant to the treatment of cancer by radiotherapy and its underlying biological mechanisms.

DPhil projects for 2019 entry

The list of DPhil projects currently available for October 2019 entry is detailed below:

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

Supervisors: Anderson Ryan, Anne Kiltie, Tim Maughan

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.

Enhancing Radiotherapy Outcomes for Oesophageal Cancer

Supervisors: Maria Hawkins; Frank Van den Heuvel.

Inhibition of ATR (a DNA damage checkpoint kinase) is currently being evaluated with radiotherapy and chemoradiation in patients with oesophageal cancer in the Cancer Research UK/MRC funded CHARIOT clinical study, whilst dose escalation is being evaluated in the SCOPE 2 clinical study.  We have done initial in silico planning to show that protons significantly reduce the dose received by heart and lung and dose modelling to predict toxicity of dose escalation. Furthermore we have shown that heart substructures have a critical role in non-cancer related mortality.  The aims of this project are:

  • to evaluate acute and late  lung and cardiac toxicity based on the radiobiological dose modelling.
  • to optimise the radiotherapy delivery strategy in the pre-operative and definitive settings for oesophageal malignancies when MRI Linac or protons are used, particularly when novel radiation sensitisers or immune modulators are incorporated into the treatment paradigm. 

The ideal applicant will have a background in radiation oncology, understanding of imaging in radiation oncology and radiotherapy planning.

Investigating the Potential Benefits of MRI-LINAC for Delivery of Stereotactic Ablative Radiotherapy (SBRT) in Hepatobiliary Malignancies

Supervisors: Maria Hawkins, Frank Van den Heuvel.

SBRT has been investigated as an alternative to conventionally fractionated radiotherapy for the local treatment of pancreatic cancer and liver malignancies. Advantages of SBRT include possibility to deliver higher biological effective doses compared to conventional radiotherapy. It has better integration with multidisciplinary treatments due to significantly shorter treatment courses, and potential immune effects. SBRT in the GI tract has potentially severe toxicity due to poor tolerance of the GI tract to radiation and the need for large margins due to poor tumour visualization and motion. Novel radiotherapy technologies (proton and MRI LINAC [MRL]) offer the opportunity to improve SBRT delivery. The project aims are:

1.     to analyse/calculate delivered dose for patients treated in pancreatic and  cholangiocarcinoma trials.

2.     to estimate potential improvement in dose delivery to tumour and normal tissue (TCP/NCTP modelling) comparing the use of motion managed LINAC, MRL or protons for pancreas and HPB malignancies,  to investigate potential benefits using novel toxicity estimation models (“duodenal unfolding”).

3.     to develop an MRL protocol including putative functional sequences to be tested prospectively for the  malignancies studied.

The ideal applicant will have a background in radiation oncology, understanding of imaging in radiation oncology and radiotherapy planning.

Determinants of Sensitivity to G-Quadruplex-Binding Compounds

Supervisors: Madalena Tarsounas, Anderson Ryan.

The observation that BRCA1 and BRCA2 deficient cells and tumours are sensitive to G-quadruplex (G4)ligands has spurred development of cancer therapies using these molecules to target homologous recombination deficiencies. The cytotoxicity of these drugs relies on binding and stabilisation of G4 structures. These, in turn, block replication fork progression and induce DNA breakage (Rodriguez et al., 2012; Zimmer et al., 2016). The precise type of DNA lesions and signalling pathways triggered by G4 ligands remain unclear. Here we propose to perform a CRISPR/Cas9 screen in human cells to identify determinants of sensitivity to G4-binding compounds. We will focus on CX-5461, a G4 ligand currently in clinical trials against tumours with DNA repair deficient tumours, including those carrying BRCA1/2mutations (Xu et al., 2017). We aim to identify a set of genes whose targeting leads to sensitivity or resistance to CX-5461 treatment. Through functional characterization of these genes, we will assemble a profile of the pathways de-regulated by this drug and how they impact on cell proliferation and survival. This approach will not only help elucidate the mechanism of action of CX-5461, but will also enable to predict tumour response and select patients likely to benefit from this specialised therapy.