Guest blog from Sally Prior who took part in FRAME’s Summer Studentship during her BSc in Medical Biochemistry at the University of Huddersfield. Sally hopes to study for a PhD in cancer biology and have a career as a cancer researcher.

During my Medical Biochemistry undergraduate degree at the University of Huddersfield, I had learnt about various experiments carried out within cancer research and had always noted that they all heavily involved the use of animals. When my tutor, Dr Anke Brüning-Richardson and I saw the online advertisement for the 2021 FRAME Summer Studentship, we both knew it would be an excellent opportunity for me to validate some imaging software, developed by Dr Brüning-Richardson and Drs Rohwedder and Knipp, whilst also exploring ways to reduce the reliance on animal derived products in the Brüning-Richardson laboratory. By focusing on targeting the ability of cancer cells to move to healthy parts of the brain, the Brüning-Richardson laboratory aims to improve the treatment of glioblastomas (GBMs), which are very aggressive and invasive cancers of the brain that re-grow after initial treatment (Ostrom et al., 2014).  

Animal use in cancer research 

Animal models have formed a huge part of cancer research for decades as they are able to mimic the characteristics of human tumours (Cekanova & Rathore, 2014), making them particularly useful for drug discovery within cancer research. However, recently the usefulness of such studies has been investigated as promising drugs from in vivo studies failed in clinical trials (Hwang et al., 2016). In addition, animal models utilised in cancer research often fall under the ‘moderate to severe’ category as outlined by the Directive 2010/63/EU (Smith et al., 2018). In brain tumour research, cancer causing chemicals are often used to induce brain tumours in mice (Huszthy et al., 2012). One of the methods classed as ‘moderate’ involves the injection or surgical placement of brain tumour cells onto the brains of healthy animals (Ozawa and James, 2010). Once brain tumours have been induced using the animal models, the effects of various drugs or treatments can then be determined. After the experiments are complete, each animal is humanely killed. 

Most scientific experiments require at least three repeats to demonstrate that the data is both reliable and accurate (Vaux et al., 2012). Each study utilising animal models could therefore contribute directly to the deaths of hundreds of animals, in particular rodents, with such experiments being carried out in institutions all throughout the UK.  

In addition, animal derived products are also commonly used in brain tumour research, with collagen from rat tails utilised in 3D invasion assays to monitor the migration of brain tumour cells from spheroids, which are mini tumours generated in the laboratory (Cheng et al., 2015). Both Dr Brüning-Richardson and I are aware of the heavy reliance on animals in brain tumour research and are very keen to explore animal–free options, especially now that Dr Brüning-Richardson has established her own laboratory at the University of Huddersfield. 

Alternatives to animal research in cancer research 

After finetuning the details of our project, which we titled ‘Validation of a Novel Software Plugin for Analysis of 3D Models of Glioma Cell Migration’, I submitted our application to FRAME. In mid-June, I received an email notifying me that I had been awarded one of the 2021 FRAME summer studentships and I couldn’t wait to get started! Throughout my summer studentship, I developed an animal-free 3D invasion assay using a new type of synthetic matrix (extracellular material that supports cells to move) for my experiments and analysed the effects of anti-migratory drugs on the migration of brain tumour cells from spheroids. This involved imaging each spheroid by confocal microscopy, where I got some amazing high-resolution images. These results demonstrated that it was possible to use an alternative to rat tail collagen in these assays, and the animal-free, synthetic matrix supported the migration of the brain tumour cells. 

The image of every spheroid was then inputted into the newly developed Cloudbuster software (Rohwedder et al., 2022, submitted to Interface Focus). I was the first person to properly use Cloudbuster, so it was very exciting to be able to use such new software and give my feedback to the developers. During my summer studentship, I was able to show that Cloudbuster could accurately determine the effects of anti-migratory drugs on the migration of brain tumour cells.  

One of the highlights of my summer research experience was having some of my work featured in a recent publication in the Biomedicines journal, titled ‘Drug Resistance in Glioma Cells Induced by a Mesenchymal-Amoeboid Migratory Switch’ (Biomedicines. 2021 Dec 22;10(1):9. doi: 10.3390/biomedicines10010009). I also recently applied to present the work from my summer studentship in the form of a poster at the British Neuro-Oncology Society 2022 conference, where I can hopefully highlight that animal-free brain tumour research is possible and looks very promising. Neither of these amazing opportunities would have been possible without my early career research experience with FRAME. 

My FRAME summer studentship opportunity was my first laboratory experience of brain tumour research, and overall, it was absolutely incredible. Although the project was only two months in total, I learned so many skills and techniques, both in and out of the laboratory, in such a short space of time. I also had lots of opportunities to network with other students and researchers, giving me a chance to learn about the exciting research being carried out at the University of Huddersfield.  

One particularly important thing I learned from my summer studentship was that lots of experiments go wrong when you try them for the first time and that’s okay.  

Not everything will work first time. It can be disheartening when you spend hours (sometimes days in my case!) setting up an experiment for it to fail, but what really matters is how you work through that failure and make it into a success.  

It’s easy to think that experiments must work first time because scientific papers mostly discuss successes, but the reality of science is full of failed experiments. 

In addition, following on from my FRAME summer studentship, I have been lucky enough to continue with the animal-free brain tumour research with Dr Brüning-Richardson in my final year research project, where I have had some very exciting findings! Carrying out my summer studentship confirmed my desire to study for a PhD and I am planning to remain within the field of brain tumour research. This would not have been possible without the amazing opportunity I was awarded from FRAME. Both Dr Brüning-Richardson and I are incredibly grateful to FRAME for funding my summer studentship. It was my first ever experience of brain tumour research and definitely set me on the path to fulfil my ambition of being a cancer researcher. It also highlighted to both Dr Brüning-Richardson and I that animal-free brain tumour research is possible, and it is as successful as traditional methods that rely on animal products.  

Overall, my FRAME funded summer studentship was an amazing opportunity that allowed me to carry out new and exciting brain tumour research, whilst confirming my desire to study a PhD and equipping me with the expertise to become a cancer researcher. 

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References 

• Cekanova, M., & Rathore, K. (2014). Animal models and therapeutic molecular targets of cancer: utility and limitations. Drug Design, Development and Therapy, 8, 1911 – 1921. https://doi.org/10.2147/DDDT.S49584 

• Cheng, V., Esteves, F., Chakrabarty, A., Cockle, J., Short, S., & Brüning-Richardson, A. (2015). High-content analysis of tumour cell invasion in three-dimensional spheroid assays. Oncoscience, 2(6), 596 – 606. https://doi.org/10.18632/oncoscience.171 
• Huszthy, P. C., Daphu, I., Niclou, S. P., Stieber, D., Nigro, J. M., Sakariassen, P. Ø., Miletic, H., Thorsen, F., & Bjerkvig, R. (2012). In vivo models of primary brain tumors: pitfalls and perspectives. Neuro-Oncology, 14(8), 979 – 993. https://doi.org/10.1093/neuonc/nos135 
• Hwang, T. J., Carpenter, D., Lauffenburger, J. C., Wang, B., Franklin, J. M., & Kesselheim, A. S. (2016). Failure of Investigational Drugs in Late-Stage Clinical Development and Publication of Trial Results. JAMA Internal Medicine, 176(12), 1826 – 1833. https://doi.org/10.1001/jamainternmed.2016.6008 
• Ostrom, Q. T., Bauchet, L., Davis, F. G., Deltour, I., Fisher, J. L., Langer, C. E., Pekmezci, M., Schwartzbaum, J. A., Turner, M. C., Walsh, K. M., Wrensch, M. R., & Barnholtz-Sloan, J. S. (2014). The epidemiology of glioma in adults: a “state of the science” review. Neuro-Oncology, 16(7), 896 – 913. https://doi.org/10.1093/neuonc/nou087 
• Ozawa, T., & James, C. D. (2010). Establishing intracranial brain tumor xenografts with subsequent analysis of tumor growth and response to therapy using bioluminescence imaging. Journal of Visualized Experiments, (41), https://doi.org/10.3791/1986 

• Rohwedder, A., Knipp, S., Esteves, F. O., Hale, M., Treanor, D., & Brüning-Richardson, A. (2022). Three-dimensional (3D) reconstruction and cloudification of immunocytochemical sections of cancer spheroids for determination of quantitative parameters. Interface Focus. 
• Smith, D., Anderson, D., Degryse, A. D., Bol, C., Criado, A., Ferrara, A., Franco, N. H., Gyertyan, I., Orellana, J. M., Ostergaard, G., Varga, O., & Voipio, H. M. (2018). Classification and reporting of severity experienced by animals used in scientific procedures: FELASA/ECLAM/ESLAV Working Group report. Laboratory Animals, 52(1), 5 – 57. https://doi.org/10.1177/0023677217744587 
• Vaux, D. L., Fidler, F., & Cumming, G. (2012). Replicates and repeats—what is the difference and is it significant? EMBO Reports, 13(4), 291 – 296. https://doi.org/10.1038/embor.2012.36