Use of proteogenomics to connect somatic mutations to signalling in breast cancer patient-derived organoids
Breast cancer is the most common cancer worldwide and there are 55,920 new breast cancer cases and 11,500 deaths a year in the UK alone. Current treatment includes surgery, radiotherapy, chemotherapy, hormone therapy and targeted therapy, which may be combined depending on the sub-type of breast cancer. At present, there is limited personalisation of the treatment options.
Thomas Kedward, a PhD student at The University of Manchester, aims to improve individual breast cancer treatment options by using breast cancer patient-derived organoid culture and proteogenomics. By using proteogenomics, researchers can gain a comprehensive understanding of the complex biological processes in an individual cancer. Thomas’ research will provide a valuable insight into the most effective treatment for each individual patient.
We speak to Thomas about his research and PhD at the Manchester Cancer Research Centre (MCRC).
Cancer used to be this nebulous term, and everyone was treated with very similar treatment regimens, but we are trying to improve this by tailoring the treatment to the patient.
PhD student at The University of Manchester
Thomas’ research involves culturing breast cancer cells derived from patient samples, as 3D structures known as organoids. He then can analyse the proteogenome of the sample to identify possible treatments, which he can then test on the cultured breast cancer patient-derived organoids. He works on cells derived from both primary tumours and metastatic breast cancer fluid samples. He hopes that this can help determine which drug is most likely to be successful for the patient that the sample was sourced from, and that this technique could be used clinically in the future.
All patients are handled and sourced via the MCRC biobank during procedures. The MCRC Biobank ensures the efficient provision of high-quality samples through its centralised infrastructure and governance framework across four NHS Trusts.
Without the use of primary samples, my project wouldn’t have the same patient-centric applications.
Coming out of school, Thomas wanted to build on his sixth form knowledge of cancer by undertaking a Microbiology degree at the University of Aberystwyth. Here he specialised in Cell, Developmental and Cancer Biology.
Following the completion of his undergraduate, Thomas studied a master’s degree in Cancer Research and Molecular Biomedicine at The University of Manchester. As part of his studies, Thomas completed two six-month placements where he gained laboratory experience that proved to be an influencing factor in proceeding with a PhD in Cancer Biology. His first placement was with Prof. C Wellbrock investigating how to overcome chemotherapy resistance in melanoma. His second placement was with Dr M Baron, investigating the non-canonical Notch signalling pathway.
Thomas began his PhD with the simple intention of wanting to help people through his love of science. His respect for the individuals and charities raising awareness for breast cancer prompted his decision to focus on the disease for his PhD.
Over the course of his PhD, Thomas has expanded his research to include the treatment of metastasis as well as primary tumours. Metastasis is the spreading of cancer cells from the primary tumour to secondary sites within the body. Commonly breast cancer spreads to the lungs, liver, brain and bones. In extremely advanced disease, cells can invade into the pleural membrane and peritoneum, causing fluid build-up. This fluid is drained as part of a patient’s care and can contain millions of breast cancer cells, which Thomas uses for his proteogenomic analysis and organoid culture approach. By including metastatic samples in his research, Thomas hopes to help identify new treatments for anyone diagnosed with advanced breast cancer.
With the use of patient samples as part of Thomas’ project, his organisational skills had to be robust and adaptable so he could coordinate with the MCRC biobank to make sure he was available for when patients were undergoing procedures. Handling and storage of patient samples also required him to be organised to ensure all samples were stored correctly.
In today’s world cancer is a really big problem and if I can help people with that then I will be really proud with that as my legacy.
Thomas was awarded the Presidential Doctoral Scholarship at the beginning of his PhD, which highlighted him as a researcher with potential to significantly impact one of the major research priorities within The University of Manchester: cancer research.
Following his PhD, Thomas believes these transferable skills will be useful in his prospective career roles.
He was selected to present his work at the European Network for Breast Development and Cancer (ENBDC) Seminar Series and a poster at the European Association for Cancer Research meeting: Goodbye Flat Biology. He has also contributed his expertise in breast cancer patient-derived organoids by co-authoring papers in the prestigious journals: Cancer Letters in 2019 & EMBO Journal in 2021.
I am thankful for the support from The University of Manchester for the Presidential Doctoral Scholarship, as it has provided me with extra opportunities to broaden my personal development by training how to manage people and projects more efficiently as part of my PhD.
Working in Cancer Research
When asked how it feels to be involved in cancer research, Thomas describes it as “the greatest honour.”
“Everyone around me is fantastic, they’re very knowledgeable and experienced. I’m just in awe of my colleagues, it really inspires me to be as good as I can be,” he explained.
Thomas expresses his love for Manchester as a city for a PhD.
“There’s always places to go, things to do, people to meet, and as a whole Manchester is great for the translational research that I am doing as there are strong links with the Christie hospital- the largest single-site cancer hospital in Europe,” he said.
Thomas describes his plans after his PhD as being very flexible. He remains open-minded when it comes to a future scientific research career but has a preference for cancer research. Ideally, he would like to build on his current PhD research and work in a post-doctoral research position in academia or in the biotech and pharma industries.
Advice for prospective PhD students
Thomas recommends doing a PhD if you have a passion for science describing it as “the culmination of that passion”.
It’s about working hard but also working smartly. Keep being organised, maintain a positive outlook and have a dynamic approach.
This article was written by MSc Science Communication Student Jessica Dullehan as part of a project placement in the Manchester Cancer Research Centre.