Inflammation is now recognised as a cardinal feature of malignancy, contributing to the development of cancer, as well as being a consequence of the disease and its treatments. In established cancers, patients with evidence of systemic inflammation have demonstrated poorer outcomes and poorer response to treatment, with inferior anti-cancer effect and greater toxicities.
Local inflammation, i.e. that arising within the primary tumour, has positive prognostic outcomes, however, as the recruitment of immune and inflammatory cells into the tumour signify a heightened immune response to the malignancy, resulting in a positive anti-cancer benefit and lower systemic inflammation.
In this flagship, we aim to examine the following aspects of cancer-related inflammation:
- Systemic vs local inflammation
- Prognostic and predictive biomarkers
- Amelioration of inflammation to improve patient outcomes
- Treatment-related inflammation, including harnessing this for better anti-cancer benefit
“Theranostics” is the name given to an emerging methodology for imaging and delivering therapy with a single compound, usually a molecule, nanoparticle or a peptide (or vector). Usually, different labels are added to the vector for pre-therapeutic imaging and for therapy. Common examples of some of the labels used are radionuclides such as PET or SPECT imaging labels (e.g., Gallium-68, Technetium-99m, Iodine-124, Copper-64) and therapy with a beta particle emitting radionuclide (e.g., Iodine-131, Lutetium-177, Yttrium-90, Copper-67). Other non-radionuclide labels that can be imaged are also available, such as fluorescent compounds. The imaging often serves to establish that the disease targeted by the therapy demonstrates sufficient uptake of the theranostic vector before proceeding with the treatment.
Flagship 2 focuses on bringing new theranostic pairs into clinical use by facilitating rapid translation from the design and pre-clinical testing phase into clinical trials & patient use. Current projects include:
- the clinical management of neuroendocrine tumours (NETs) including the development of biomarkers, Quality of Life assessments and databases to assist in defining prognostic markers, collaborating with the Pharma industry to run first-in-man imaging trials of new theranostic radiolabel pairings and new peptide antagonists,
- providing an appropriate trial framework for introducing new theranostics to examine their efficacy and applying new imaging methodologies to better inform treatment decisions (g., in lymphoedema, functional pituitary lesions, brain tumours),
- developing new radiolabelled forms of anti-cancer pharmaceuticals to image with prior to therapy to demonstrate in vivo targeting,
- studying the sequencing or combination of therapies combining chemotherapy and immunotherapy with a theranostic approach.
The broad purpose of Flagship 4 is to embed/define nanotechnology in oncology. The Flagship brings together several disciplines, some non-medical, across multiple sites and multiple partners to enhance capacity at SV. Its primary aim is to better define lymph-node metastasis in colorectal cancer with a view to developing a nanotechnology-based theranostic pathway. A secondary aim is to improve adenoma recognition at colonoscopy by developing a surface biomarker based nano-beacon.
“The intertwined fates of inflammation and coagulation in glioma” Cho, A., McKelvey, K., Lee, A. and Hudson, A.
“Radiation, inflammation and the immune response in cancer” Back, M., Diakos, C., Eade, T., Hudson, A., and McKelvey, K.
“Nanoparticle radio-enhancement: principles, progress and application to cancer treatment” Zdenka Kuncic and Sandrine Lacombe
“Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol” A L McNamara, W W Y Kam, N Scales, S J McMahon, J W Bennett, H L Byrne, J Schuemann, H Paganetti, R Banati and Z Kuncic
“Cancer nanomedicine: challenges and opportunities” Zdenka Kuncic