Congratulations on your tenure as Chief Clinician at Cancer Research UK, what achievements are you most proud of over that time?

Proud is a strong word, as there is nothing I have done alone – it has been thanks to a large team at CRUK that we have made progress including thanks to my friends and colleagues Karen Vousden, KJ Patel, Iain Foulkes and David Scott.

I am most excited about the work we have done at CRUK to enhance clinician scientist training across all stages of career development. I am also really pleased to have been part of bringing the importance of viewing cancer as a systemic disease rather than a cancer cell intrinsic process to the challenges set for Cancer Grand Challenges. It has also been great to help underscore the importance of bringing discovery science to the core of all we do in funding through multiple committees at CRUK, including our Clinical research and Population committees.

Your research has been instrumental in shaping our understanding of tumour heterogeneity and cancer evolution. How has the field progressed over the past decade?

The field has moved from describing heterogeneity to quantifying and modelling it.

A decade ago, multi-region sequencing was still novel. Today, we can reconstruct phylogenies, time mutational processes, measure clonal selection under therapy, and detect residual disease at parts-per-million sensitivity.

We now understand that metastasis is often seeded earlier than we once thought, relapse frequently arises from rare resistant subclones present at diagnosis and the immune microenvironment co-evolves with tumour clones. We also know that tumour clones evolve to evade immune pressures, and mutational processes shape evolutionary trajectories in predictable ways. Importantly, we’ve also learned that truncal, ubiquitous alterations represent rational therapeutic targets, whereas subclonal diversity underpins resistance.

That conceptual shift, from treating ‘the tumour’ to targeting the evolutionary trunk, is influencing both drug development and vaccine strategies. But we’re still only beginning to understand how environmental exposures, inflammation, and ageing shape the earliest stages of tumour initiation. In my view that’s where the next frontier lies.

As cancer research becomes increasingly data‑driven and collaborative, where do you see the biggest opportunities for translating cutting‑edge discoveries into patient benefit?

The opportunities are exciting. We now generate longitudinal, multi-omic datasets at unprecedented resolution. If integrated properly, these allow us to move from reactive treatment to risk prediction, interception, and adaptive therapy.

Minimal residual disease detection is a good example. With highly sensitive personalised assays, we can identify molecular relapse months before clinical recurrence. This opens up huge opportunities in the adjuvant clinical trials setting to identify and escalate therapy in patients most at risk. That opens the door to intervention at a stage when tumour subclonal burden is low and chance of cure is higher.

With this chapter closing, how do you envision your own work evolving?

I am incredibly excited about cancer prevention and want to dedicate the next 10 years to working in this field. By understanding the earliest molecular events that drive tumour initiation, we are beginning to glimpse the possibility of molecular cancer prevention – identifying high-risk clonal expansions or inflammatory states and intervening before invasive disease ever develops.

What has become increasingly clear is that many environmental exposures may not act primarily as mutagens, but as promoters. In a cancer promotion model, selective expansion – where inflammation, metabolic stress, or environmental stimuli create a permissive niche – allows pre-existing mutant clones to expand and acquire further malignant traits. If we can identify and modulate those promoting signals, for example chronic inflammatory pathways or tissue repair programmes that drive progenitor cell plasticity, we may be able to prevent progression even when mutations are already present.

Prevention, in this sense, becomes an evolutionary strategy. Rather than trying to eliminate every mutation, we aim to suppress the ecological conditions that allow dangerous clones to dominate. The ambition is not simply earlier diagnosis, but biological interception: altering the trajectory of cancer evolution before metastatic competence is established.

Looking to the future of oncology more widely, what developments give you the greatest optimism?

The power of discovery research never ceases to amaze and inspire me. Just when you think a particular area of medicine is hopeless, breakthroughs occur that change the way we think about disease.

I have seen this happen multiple times during my oncology career, from targeted therapies hitting HER2 and EGFR through to cancer immune-therapy achieving cures in metastatic melanoma. Then there was the early detection of lung cancer through low dose CT screening, and the development of a better understanding of which patients need – and benefit from – adjuvant therapies.

It really does show the power of investment in discovery research in driving better cancer outcomes.