I am a Clinician Scientist in Clinical Oncology undertaking both laboratory and clinical research. I run a research laboratory focused on improving the efficacy of radiotherapy by developing treatments that specifically make tumour cells more sensitive to radiotherapy. The ultimate aim of this work is to develop treatments to improve the ability of radiotherapy to cure patients without increasing side-effects.
Our work often involves developing new drug treatments in combination with either commercial partners or academic collaborators within the University of Oxford.
In the clinic, I treat lung cancer patients with radiotherapy, chemotherapy and immunotherapy. I lead clinical trials that translate our most promising laboratory findings into patient studies.
I have significant experience in undertaking clinical trials relevant to radiotherapy and am the Clinical Director of the CRUK Oxford RadNet centre. My clinical trials typically incorporate novel functional imaging of the tumour microenvironment (e.g. perfusion CT, OE-MRI & hypoxia PET-CT) and I am joint-lead investigator of the “National Cancer Imaging Translational Accelerator” (NCITA) award from CRUK.
We have previously identified therapeutic targets which modulate “intrinsic” radiosensitivity by altering processes such as DNA damage repair (eg DNA Polymerase Theta), or intracellular signalling (eg TOPK). This has led to the development of large-scale drug development programmes which have successfully been adopted by commercial collaborators such as Artios Pharma.
In addition, we have also identified treatments that effectively alter the tumour microenvironment. For example, we have previously found that the safe and widely used antimalarial drug atovaquone inhibits oxidative phosphorylation, reducing hypoxia, and leading to tumour radiosensitisation.
I am currently the Chief Investigator for two clinical trials:
- The ARCADIAN trial (Atovaquone with Radical ChemorADIotherapy in locally Advanced NSCLC) follows on from our laboratory work identifying atovaquone as a novel radiation sensitiser and leads on directly from our previous proof of concept trial (ATOM) demonstrating the ability of this drug to reduce tumour hypoxia in lung cancers.
- The FIG trial (18F-FDOPA PET imaging in GLIOMA: feasibility study for PET guided brain biopsy) is investigating the benefit of using an amino acid PET tracer to more accurately identify low and high grade gliomas (https://ncita.org.uk/exemplar-7).
Since our research incorporates laboratory work as well as cancer imaging studies and radiotherapy trials, my group comprises individuals with diverse academic backgrounds:
Gonzalo Rodriguez-Berriguete, Postdoctoral Researcher
Rathi Puliyadi, Research Assistant
Puru Thambiayah, DPhil student
Nicole Machado, MRes Student
Joseph Boen, MRes Student
Daniel McGowan, Postdoctoral Researcher
Joy Roach, Clinical Research Fellow (DPhil student)
Martina McAteer, Engagement Manager (NCITA)
Edith Gallagher, Research Radiographer
- Rodriguez-Berriguete, G. et al. (2022) Small-molecule Polθ inhibitors provide safe and effective tumor radiosensitization in preclinical models, BioRx (Preprint).
- Skwarski, M. et al. (2021) Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non-Small Cell Lung Cancer, Clinical Cancer Research, 1;27(9), pp. 2459-2469.
- Herbert, K. et al (2021) Targeting TOPK sensitises tumour cells to radiation-induced damage by enhancing replication stress, Cell Death & Differentiation. 28, pp. 1333–1346
- McGowan, D.R. et al. (2019) Buparlisib with thoracic radiotherapy and its effect on tumour hypoxia: A phase I study in patients with advanced non-small cell lung carcinoma, European Journal of Cancer, 113, pp. 87-95
- Herbert, K. et al (2018) T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics, Cell Death & Disease, 9(1089)
- Higgins, G.S. & Boulton, S.J. (2018) Beyond PARP-POLθ as an anticancer target, Science, 16;359(6381), pp. 1217-1218
- Ashton, T. et al. (2018) Oxidative Phosphorylation as an Emerging Target in Cancer Therapy, Clinical Cancer Research, 1;24(11), pp. 2482-2490
- Ashton T. et al. (2016) The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia, Nature Communications, 7(12308)
- Higgins, G.S. et al (2015) Overexpression of POLQ confers a poor prognosis in early breast cancer patients, Oncotarget, 6, pp. 8244-8254
- Higgins, G.S. et al (2010) A small interfering RNA screen of genes involved in DNA repair identifies tumor-specific radiosensitization by POLQ knockdown, Cancer Research, 1;70(7), pp. 2984-93