Professor Fiona Thistlethwaite
Medical Oncology Consultant, The Christie NHS Foundation Trust, and Honorary Professor, Division of Cancer Sciences, University of Manchester
Meet Fiona Thistlethwaite. After finishing her MB-PhD programme at The University of Cambridge in 1999, Fiona completed various training posts at the Royal Liverpool University Hospital, The Royal Marsden NHS Foundation Trust and The Christie NHS Foundation Trust.
Fiona became a consultant at The Christie in 2007 and her academic focus is clinical trial development in immunotherapy and adoptive T-cell therapy. Fiona leads the Manchester health consortium, iMATCH, which was awarded almost £9 million by Innovate UK to ensure that more patients benefit from a new generation of advanced cell therapies. As Medical Director of the Manchester NIHR Clinical Research Facility at The Christie, she oversees the delivery of over 400 clinical trials for cancer patients. Fiona is also an Honorary Professor in the Division of Cancer Sciences at The University of Manchester.
We spoke to Fiona to learn more about her career journey, research, and advice to prospective MB-PhD students.
Can you tell us about your academic background and your experience in the MB-PhD programme at The University of Cambridge and later training posts?
I participated in the MB-PhD programme at The University of Cambridge in the 1990s. At that time, it was the only such programme in the UK. I completed a pre-clinical undergraduate degree before beginning my clinical training. After one year of clinical work as a medical student, I took three years out to undertake a PhD, with some clinical attachments to maintain my skills, before returning to finish my clinical training.
It was an amazing experience! I received a lot of support in finding a PhD project, including help arranging meetings with group leaders. Because the programme included funding, I was able to approach labs and have open discussions about potential projects. I eventually joined Martin Evans’s lab at The University of Cambridge, where he was carrying out pioneering work on mice gene knockouts to study the effects of mutating a particular gene.
Initially, I had a general interest in genetics and had considered clinical genetics as a career. What I realised through my MB-PhD though was that cancer is genetic, both in the sense of germline genetic changes and genetic changes within the tumour itself. In the 1990s, we were just beginning to identify that if these genetic changes affect proteins and downstream events in the cell, then we might be able to specifically inhibit the abnormal pathways with drugs to produce an anti-cancer effect. That idea that genetic changes could be interfered with to achieve an anti-cancer effect was a novel concept at the time and really attractive to me.
My work involved knocking out a gene called BRCA2, one of the breast cancer genes. At the time, the gene had only just been cloned in humans, and we didn’t yet have the mouse equivalent or know its sequence. So my first job was to figure that out, and then to knock out the gene in mice and see what the effects were. I spent about two years doing the mouse knockout, and then subsequently analysing the phenotype of the mice. After completing my MB-PhD, I returned to clinical work at The University of Cambridge, completed my house jobs, and later moved to Manchester for specialist registrar training.
Your MB-PhD project explored molecular mechanisms in inherited breast cancer syndromes. What sparked your interest in this research area?
The project was identified partly because the human genome had just been cloned, and there was a growing understanding of its role in familial breast cancer. We thought it could be important to knock it out in mice to study its function. At the time, I was very early in my medical career — I didn’t come in specifically interested in breast cancer, but rather with a broader interest in genetics and how it might be applied in an oncology setting.
One of the things that really appealed to me about doing a PhD is that you have the opportunity to become a world expert in a tiny niche area of science. In fact, you probably know as much, or even more, than anyone else about that particular area. And that was a real source of motivation for me to study an MB-PhD.
Professor Fiona Thistlethwaite
What were the biggest challenges you faced while balancing medical studies with a MB-PhD, and how did you overcome them?
During my MB-PhD, the timeline was tightly defined. The day I started my PhD component, I knew the exact date I would return to clinical training, which meant I couldn’t spend much time settling in, as I needed to start generating results quickly. But in many ways, having a clear and defined timeline for the MB-PhD was a good thing, as it enabled me to stay focused.
One of the biggest challenges for me came after my MB-PhD. In the 1990s, there was very little set up in terms of mentorship or understanding of how to progress our careers beyond the PhD. I went back into clinical practice and took a training post quite far from where I’d done my research, so I didn’t have the opportunity to go back into the lab or continue the work as a postdoc. It was up to me to maintain or develop links with laboratories. That was a particular challenge at the time, but it’s something that has changed enormously — there’s now much stronger mentorship and support to help with your subsequent career development, especially here in Manchester.
Looking back, what aspects of the MB-PhD experience do you feel were most valuable for your career development?
Doing an MB-PhD gave me a great head start in planning my career. It not only shaped my career goals, as it was during the programme that I realised oncology was what I was passionate about, but it also put me one step ahead of others when applying for training posts and competing for positions. I had the opportunity to be lead author on some publications, which was also a great asset to my CV.
My career has been in early-phase trial development and drug development. Without doing a molecular-based MB-PhD I don’t think I could have taken scientific concepts from the lab directly into the clinic to test new drugs and complex therapies, especially in first-in-human trials.
How has your MB-PhD training influenced your journey as a clinician-scientist?
My MB-PhD involved molecular biology and laboratory-based work, like sequencing genes and wet lab work. The training I received on the programme allowed me to better understand the science behind our research and the practicalities of using models to study human diseases and develop new treatment concepts.
Although I don’t have my own lab group, my MB-PhD training enabled me to ‘speak the same language’ as scientists, develop research ideas and studies, and translate them into clinical applications.
What achievements are you most proud of in your career so far? Are there any pivotal moments or stories that stand out?
The achievement I’m most proud of is being able to treat patients who were previously told their cancer had spread and that they had a very short life expectancy. Through treatments, especially immunotherapies, we’ve seen some patients respond exceptionally well, with their disease disappearing and never coming back. When I started my career, the idea of curing patients with metastatic disease wasn’t a concept, so being a small part of developing drugs that have made this possible is really amazing.
My advice would be to speak to as many people as possible about potential projects and choose one that you’re truly passionate about. Doing an MB-PhD is challenging, so you need to be deeply interested in the area you’re studying. Select your project carefully.
Professor Fiona Thistlethwaite
What are your aspirations for the future of cancer research and immunotherapy, and do you have any career goals you still hope to achieve?
Despite recent progress, we’ve still got a long way to go. I think the rest of my career will focus on identifying who can benefit from specific drugs and selecting the right treatment for each patient. We now recognize the immune system’s central role in cancer but its complexity means not all patients respond to immunotherapy. The future lies in better understanding that complexity — selecting the right therapies for the right patient and combining therapies where needed.
What advice would you give to medical students or aspiring cancer researchers considering an MB-PhD?
My advice would be to speak to as many people as possible about potential projects and choose one that you’re truly passionate about. Doing an MB-PhD is challenging, so you need to be deeply interested in the area you’re studying. Select your project carefully. I don’t regret doing my PhD early, as it gave my career a significant boost. However, it’s also important to think about what comes after your PhD. Consider whether you want to do a postdoc, where you want to be based, and how you can continue your academic development. So, think about what comes after the PhD, as well as the PhD itself.
How can MB-PhD students make the most of their training and research opportunities?
There are far more opportunities for PhD students now than when I did mine in the 1990s. I essentially went into a lab and came out three years later with some research experience. Now, universities offer so much more support – from short courses in artificial intelligence to training in biostatistics and bioinformatics. I would grasp all those opportunities if you can, because they’re important, not just for developing your lab-based research, but also for shaping your career as a clinician. They’ll set you apart when you start to compete for jobs!
