PROJECT TITLE: Single-cell transcriptomics linked to lineage tracing to interrogate the role of intra-tumour heterogeneity in shaping therapeutic susceptibility and resistance in paediatric cancer
LEAD INVESTIGATOR: Dr Alejandra Bruna
INSTITUTION: The Institute of Cancer Research
AWARD APPROX: £500,000 (funded by The Little Princess Trust in partnership with CCLG)
Neuroblastoma is one of the most common types of childhood cancer and is particularly good at adapting to resist treatment. When we take a closer look at a neuroblastoma tumour, we discover something extraordinary – they’re made up of lots of different types of cells, each with unique traits and behaviours. Due to this, there are a wide range of outcomes for patients, with some rare cases of neuroblastoma spontaneously curing themselves, while others can be incurable.
Neuroblastoma cells can adapt to their surroundings using a trait called ‘phenotypic plasticity’, which lets the cells change how they look or behave without affecting their genetic code. The cancer cells seem to exploit their differences to navigate the challenges posed by treatment. By doing so, they persist, adapt and ultimately re-emerge as a relapsed disease, often with limited treatment options.
What this means for neuroblastoma treatment
The diversity hidden within neuroblastoma tumours holds a key to improving their treatment. Understanding this diversity could help doctors target specific cell types within tumours, potentially significantly improving outcomes. However, if neuroblastoma keeps changing over time, a truly effective approach could be one that prevents this transition process. Understanding the dynamics of cancer evolution is a key priority according to recent studies, especially in childhood cancers like neuroblastoma. These studies go against traditional beliefs that mutations in the genetic code are the primary drivers of cancer evolution and suggest that non-genetic variation like phenotypic plasticity play a crucial role.
By understanding the types and origins of neuroblastoma diversity, researchers are better equipped to devise strategies that target the tumour’s adaptability. We predict that targeting the most adapted cell state and the process of adaptation itself would be an effective way to cure neuroblastoma.
Our mission in the lab
In our laboratory, we want to understand how neuroblastoma evolves. We’re harnessing a cutting-edge technology called ‘single-cell barcoding’, which allows us to look at the cells we have grown in the lab and see how they evolved with treatment and other stages of neuroblastoma. Our goal is to gather evidence of the nongenetic drivers behind cancer evolution.
Additionally, we’re in the process of developing special tools that can identify biomarkers in the body linked to non-genetic treatment responses. These biomarkers could significantly impact outcomes by helping doctors choose more effective treatments.
Anticipating progress and personalised care
Our research not only aims to uncover the mysteries of cancer evolution but also holds the promise of personalised care for neuroblastoma patients. By understanding which patients are likely to be unresponsive to treatment, experience progression, or face relapse, we aim to provide doctors with vital predictive information. Armed with this knowledge, we can work towards strategies to prevent resistance and relapse.
In conclusion, the significance of understanding non-genetic diversity in childhood cancers like neuroblastoma can’t be overstated. Our journey into the complexities of cancer evolution has the potential to transform the way we approach treatment, prediction and patient care. Through a combination of advanced technologies and innovative thinking, we hope to pave the way for improved outcomes and brighter futures for young patients and their families.
From Contact magazine issue 102 - Spring 2024
