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Queen’s University Belfast
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Everything happens in 3’s – A trilogy of Preclinical Radiotherapy Research from Belfast

Recently, the Radiobiology Research Group from the Centre for Cancer Research and Cell Biology at Queen’s University Belfast published a series of articles using SARRP to explore different translationally focused experimental approaches. The group, led by Prof Kevin Prise and Dr Karl Butterworth, have published three back to back papers within three months which reflect the interests of the research program in nanoparticle theranostics, bystander signaling and novel combination therapy.

In the first paper (Butterworth et al, Nanomedicine, 2016) evaluated DTDTPA conjugated GNPs in a human prostate xenograft model to demonstrate enhancement of CBCT and tumor growth delay. They concluded that when used in an appropriate clinical context, GNPs hold significant potential as theranostic agents for radiotherapy. Furthermore, surface conjugation with DTDTPA provided protection against agglomeration and protein absorption, whilst yielding potent radiosensitizaton. The article can be found at: https://www.ncbi.nlm.nih.gov/pubmed/27463088.

Providing mechanistic insight in underlying radiobiological response mechanisms is part of the overall goal of translational radiobiology research. Spatially fractionated radiation therapy (SFRT) using grid geometries is clinical technique in which radiotherapy is delivered through small openings to provide effective tumor control whilst sparing normal tissue. The second paper (Butterworth et al, Br J Radiol. 2016) positioned SARRP at the center of a modelling study to determine potential impacts of bystander signaling for different spatially fractionated dose distributions. Historically, it has been understood that homogenous dose distribution to the tumor target is the optimum form of treatment, however, in this study highly heterogenous dose distributions caused greater cell kill. Overall, the authors demonstrated the impact of radiation induced signaling on tumor cell response for SFRT and identified key experiments parameters to validate the propose model. The article can be found at: https://www.ncbi.nlm.nih.gov/pubmed/27557131.

In the last installment of the trilogy from Queen’s (McLaughlin et al, Mol Cancer Ther. 2016), the group evaluated a novel target for combined therapy in non-small cell lung cancer (NSCLC), the endogenous capase-8 inhibitor, FLIP. Data showed significant enhancement of cell death after ionizing radiation when FLIP protein levels were downregulated via RNAi. Furthermore, HDAC inhibitors were found to sensitized NSCLC cells to radiation dependent on their ability to suppress FLIP and promote activation of capase-8. These data were confirmed in vivo where Entinostat, a well-known HDAC inhibitor, enhanced antitumor activity. Overall, the authors concluded that FLIP downregulation induced by HDAC inhibitors is a potential clinical strategy in radiotherapy for NSCLC. The article can be found at: https://www.ncbi.nlm.nih.gov/pubmed/27474150.

In conclusion, these articles exemplify SARRP applications in a translational research setting. The data from the studies focusing on addressing challenges in radiation oncology that ultimately have potential to improve patient outcomes. As a research community, it’s important to consider clinical issues and optimize experimental radiobiology approaches in this context. For more information on these studies or enquiries about the SARRP radiobiology program at Queen’s University Belfast, please contact either Dr. Karl Butterworth or Prof. Kevin Prise.

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