Vision & Strategy

Applying Cancer Discovery to Patient Benefit

At the CRUK Scotland Institute, our overarching vision is to make pioneering discoveries that increase our understanding of cancer; build collaborative, multidisciplinary teams that drive progress towards clinical translation; and train the next generation of diverse and leading cancer researchers.

By understanding the fundamental mechanisms that drive cancer, both at early and late stages of the disease, we aim to uncover new preventative and therapeutic approaches for the benefit of patients. To do this, we are addressing three fundamental cancer challenges:

• Biology of early disease (How cancers start): How can we detect cancer earlier, identify factors leading to poor prognosis (‘bad actors’) and design preventative strategies?
• Energetic needs and metabolism (How cancers grow): What are the novel therapeutic vulnerabilities associated with increased energetic stress in tumours cells; either alone or following chemotherapy?
• Metastasis and microenvironment (How cancers spread): What are the therapeutic vulnerabilities of metastasising cancers and disseminated disease, and what is the impact of the immune system on metastasis?

At the heart of our strategy is the generation and use of an unparalleled suite of complex in vivo and organoid models that accurately recapitulate critical events in the human disease - such as tumour initiation, growth and metastasis (Figure 1). To achieve this effectively, we have put particular emphasis on ensuring that our in vivo models are extensively and rigorously benchmarked against the appropriate human cancers, their pathology, and co-morbidities – something we term ‘disease positioning’. The recent explosion in technologies (including single cell RNA sequencing, spatial transcriptomics and metabolomics, multiplexed imaging and computational biology) to probe tissue deeper than ever before, allows our in vivo models to be comprehensively disease positioned and supports an approach allowing close integration of our mechanistic biology with human disease cohorts (for forward and back translation). In future, a greater understanding of the impact of host physiology could also revolutionise our approach to treating and detecting cancer. Factors such as diet, age, temperature, obesity and microbiome can have profound effects on the initiation and progression of cancer. We believe that by studying these processes in our disease relevant models, we can better understand how they affect tumour biology from a whole-body perspective.

We are focusing our efforts on key tumour types to translate our targeted observations, some of which are defined by CRUK as cancers of unmet need (liver, pancreas, lung), are specifically relevant to our local population (mesothelioma) and/or are high contributors to cancer-related death (colorectal). We are focusing on liver and lung as sites of metastasis and on insights that will arise from cross-comparing primary and metastatic growth. These studies are supported by our excellent technology platforms, which we will need to maintain and invest in to remain state-of-the-art. With the tumour specific focus of CRUK Scotland Centre, we have excellent clinical support to be able to translate our finding from our models into the clinic.

Partnership is a key objective of our strategy, and we believe we are the world’s foremost partner of choice for models, imaging and energetic stress collaborations for both academia and industry. Therefore, over the next five years, we aim to extend our research into cancer as a whole-body disease in partnership with the CANCAN (lead Eileen White, co-investigator David Lewis) and OPTIMISTIC Cancer Grand Challenge teams (lead Wendy Garrett) to drive forward our exploration of cancer cachexia and the microbiome, respectively. These programmes of work will allow us to investigate inter-organ communication and the whole organism in both early and late disease. In collaboration with the MRC National Mouse Genetics Network, we are also planning to make a step-change in ‘humanisation’, phenotyping and therapeutic targeting in mouse models. We are aiming for new alliances with industry in the energetic stress, metastatic targeting and disease-positioning space.

To deliver this exciting and highly relevant strategy, we have defined some specific objectives in areas where we feel we are ideally placed to make a clear impact in the next five years and where we will aim target our efforts and resources:

1. Becoming a centre of excellence for liver cancer and metastasis
2. Making a step change in mouse models
3. Targeting protein turnover to block initiation and progression
4. Targeting energetic stress and tumour microenvironment following radiotherapy
5. Determining the impact of mitochondrial mutations in initiation and progression
6. Building a greater understanding of cancer immunology
7. Revolutionising computational biology