Paving the way
Read more about how SPECIFICANCER’s discovery research is poised to enter clinical trials.
SPECIFICANCER: the team that took on the tissue specificity challenge
Currently viewing section: The challenge
The challenge
The tissue specificity challenge was set in 2017, to understand why despite being expressed in a wide variety of tissues, some cancer genes contribute to tumorigenesis only in certain tissues but not in others. For example, why mutations in the BRCA1 and BRCA2 genes are only implicated in breast and ovarian cancer, when faulty genes are present in nearly all cells within the body.
It was expected that solving the challenge would identify the biological mechanisms underlying tissue specificity and inform future approaches to prevent or treat cancer. The SPECIFICANCER team hypothesised that the epigenetic landscape of a tissue, laid down during development, determined the tissue specificity of cancer driver genes.
Reshaping understanding of tissue specificity to pioneer novel combination therapies
The team’s fundamental findings revealed manipulating cell state opens up therapeutic opportunitiesSPECIFICANCER’s impact
Over the course of its funding the SPECIFICANCER team has uncovered important insights into tissue specificity, helping to understand what makes a tissue permissive or not. The team has identified the rules of RAS, what underlies Wnt pathway permissivity, oestrogen receptor tissue specificity and the role of the adaptive immune system in driving tumour suppressor inactivation. Overall, the team’s work proved that tissue specificity indeed comes from a cell’s epigenetic environment, which allows cancer drivers to signal in such a way that confers an advantage.
As well as identifying novel biological mechanisms, the team has shown across tumour types the success of a critical combination of inhibitors, epigenetic and oncogenic, which first drive differentiation to then allow execution of tissue specific developmental cell death pathways. The team is poised to start multiple clinical trials based on its discovery science and hope to translate its findings into better outcomes for patients. SPECIFICANCER’s work and creative therapeutic approaches also contributed towards Cancer Grand Challenges setting the rewiring cancer cells challenge in 2025.
