Our research focuses on finding new ways of making tumours more sensitive to radiotherapy treatment.
Although radiotherapy is effective at curing many different types of cancer, some tumours are recognised as being resistant to radiation treatment.
The presence of genetic and epigenetic changes in tumour cells can lead to ‘intrinsic radioresistance’, whilst the presence of an abnormal tumour microenvironment such as tumour hypoxia can lead to ‘extrinsic radioresistance’
Our laboratory research has involved large-scale drug and siRNA screens to find new ways of increasing tumour radiosensitivity. Our aim is to use these findings to develop treatments that can be combined with radiotherapy to improve outcomes for cancer patients.
We aim to translate our laboratory findings into clinical trials with a particular emphasis on lung cancer. Radiotherapy plays a key role in the management of lung cancer yet this disease is still associated with poor outcomes.
Our trials often involve the use of functional imaging, such as perfusion CT scans and 18F-Misonidazole PET-CT scans, to detect changes in tumour blood flow and regions of tumour hypoxia, respectively. By performing these scans before and after drug treatment we can assess whether hypoxia has been reduced in the tumour, making it more likely to respond favorably to radiotherapy.
Figure legend: 18F-Misonidazole PET-CT scan showing a large left upper lobe tumour with lymph node metastases. Hypoxic areas of the tumour are represented by red regions on the scan.
Geoff Higgins is an Associate Professor in the CRUK/MRC Oxford Institute for Radiation Oncology, having held a Cancer Research UK Clinician Scientist award since 2011. He is an Honorary Consultant Clinical Oncologist in Oxford University Hospitals NHS Trust and is a Medical Research Fellow at Corpus Christi College. He previously undertook specialist medical training at the Edinburgh Cancer Centre before moving to Oxford as a Cancer Research UK Clinical Research Fellow in 2007.
Atovaqone decreases oxygen consumption of tumour cells, reducing hypoxia and inducing tumour radiosensitisation. Ashton T et al. Nat. Commun. 2016 25;7:12308
18F-Misonidazole PET-CT scan detection of occult bone metastasis. McGowan D et al. Thorax 2016;71(1):97
Identification of Vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen. Tiwana GS et al. Oncotarget. 2015;6(8):5978-89
Drug Radiotherapy Combinations: Review of previous failures and reasons for future optimism. Higgins GS et al. Cancer Treat Rev. 2015 Feb; 41(2):105-113A Small Interfering RNA Screen of Genes Involved in DNA Repair Identifies Tumor-Specific Radiosensitization by POLQ Knockdown. Higgins GS, Prevo R, Lee YF, Helleday T, Muschel RJ, Taylor S, Yoshimura M, Hickson ID, Bernhard EJ, McKenna WG. Cancer Res 2010; 70 :2984-93.
Martin-Immanuel Bittner, DPhil Student
James Coates, DPhil Student
Giovanna Granata, DPhil Student
Katharine Herbert, Postdoctoral Researcher
Daniel McGowan, Postdoctoral Researcher
Rathi Puliyadi, Research Assistant
Gonzalo Rodriguez-Berriguete, Postdoctoral Researcher
Michael Skwarski, Clinical Research Fellow