Paul O’Gorman Building, University College London,
72 Huntley Street, London, WC1E 6DD
United Kingdom

The Witney Group at UCL's Centre for Advanced Biomedical Imaging. Specialising in the development of advanced cancer imaging tools.

M2_UT_VRT.PNG

Projects

Imaging therapy resistance in OVARIAN cancer

Monitoring the acquisition of therapy resistance in cancer is a pressing and unmet clinical challenge.

Resistance to chemotherapy and molecularly-targeted therapies provides a major hurdle for cancer treatment due to the underlying genetic and biochemical heterogeneity of tumours. Despite intensive research, the field has struggled to provide a solution for sensitive and specific molecular imaging of tumour response and resistance to therapy.

Ovarian cancer remains a leading cause of death worldwide, with a 10-year survival rate of just 35% [1].  First-line platinum-taxane chemotherapy yields high initial response rates, however patients often relapse with drug-resistant disease [2]. At the moment there is no satisfactory way to predict which patients will to respond to therapy upon relapse. A new diagnostic imaging test that can predict platinum resistance at the point of relapse will enable patient stratification, enabling the clinician to select the most appropriate second-line therapy for the individual patient using a precision medicine approach. Where no suitable treatment options are available, patients with resistant disease will no longer receive inappropriate second-line treatment, thus avoiding associated side effects; resulting in substantially improved quality of life and the opportunity to initiate palliative care at an earlier stage.

Employing a combination of innovative preclinical imaging and metabolomic strategies, we are developing new tools to noninvasively assess the mechanisms that tumour cells employ to resist treatment. Working across the disciplines of oncology, biochemistry and molecular imaging, this collaborative approach between University College London and the Francis Crick Institute will investigate the role of altered tumour metabolism as an indicator of drug resistance. Specifically, we are developing novel positron emission tomography (PET) imaging techniques to investigate altered tumour metabolism. PET captures images of high-energy gamma-rays that are emitted from inside a subject following intravenous administration of a radioisotope-tagged molecule, termed ‘radiotracer’. Using a similar approach, we have previously used PET to image the rate-limiting enzyme in tumour glycolysis [3], deregulated glycogen synthesis [4], fatty acid β-oxidation [5], and choline metabolism [6] that are associated with malignant transformation. Importantly, the the molecular imaging tools developed as part of this project are not confined to ovarian cancer, but have the potential for widespread impact in cancer management for many other cancer types.

Strategy for the noninvasive detection of tumour resistance to therapy using radionuclide imaging. Figure adapted from Nguyen, Q.D. & Aboagye, E.O. Integr Biol 2:483-95

Strategy for the noninvasive detection of tumour resistance to therapy using radionuclide imaging. Figure adapted from Nguyen, Q.D. & Aboagye, E.O. Integr Biol 2:483-95

[1] Cancer Research UK, 2012.

[2] Coleman, M.P., et al., 2011. Lancet 377(9760): p. 127-38.

[3] Witney et al., 2015. Sci Transl Med. 7(310): 310ra169.

[4] Witney et al., 2014. Cancer Res 74(5): p. 1319-28.

[5] Witney et al. 2014. J Nucl Med 55(9): p. 1506-12.

[6] Witney et al. 2012. Clin Cancer Res 18(4): p. 1063-72.

 

Tumour redox imaging

Investigating the fine balance between the synthesis of intracellular antioxidants and drug-induced oxidative stress.

World Molecular Imaging Congress Young Investigator of the Year 2017 project

Tumour cells employ a multitude of mechanisms to protect them from drug-induced cell death. One such mechanism is the upregulation of the body's main antioxidant, glutathione. Working in collaboration with our Industrial Partner, Piramal Imaging, we are seeking to understand how cancer cells aberrantly regulate glutathione biosynthesis as a response to drug-induced oxidative stress. Imaging provides unrivalled temporospatial information regarding tumour redox status, with important clinical implications as to whether the tumour lives or dies following therapy.