Cancer Grand Challenges is a series of £20m ($25m) awards that give international teams of researchers the freedom to think differently, act creatively and explore truly innovative science to take on fundamental questions in cancer.
This was a challenge in an earlier round, we are not currently accepting applications for this challenge.
In recent years molecular profiling has transformed our understanding of the genes that are dysregulated or mutated in specific tumour types. However, there remains a simple but confounding question of why, despite being expressed in a wide variety of tissues, some cancer genes contribute to tumorigenesis only in certain tissues but not in others. This is observed in hereditary cancer predisposition syndromes whereby, for example, germline mutations in BRCA1 and BRCA2 primarily cause breast and ovarian cancers. It also extends to somatic mutations where aberrations in cancer genes are frequently observed in some cancers but not others, for example APC in colorectal cancer and KRAS in pancreatic cancer.
The mechanisms that determine the tissue specificity of cancer genes remain poorly understood but are likely to be multifactorial including intrinsic, extrinsic and environmental factors. Further biological insights into these pathways could enable the development of novel preventative and/or therapeutic interventions for specific cancer types.
Barriers and opportunities
This Cancer Grand Challenge calls for innovative approaches to elucidate the underlying biology responsible for the observed tissue specificity of cancer genes, with the intention to use this knowledge to develop novel preventative or treatment strategies. Given the current lack of insight on the topic, there an opportunity for teams to present ambitious and powerful mechanistic approaches to address this challenge in unexpected ways. Examples of the types of questions that could be addressed in this challenge include (but are not limited to):
- Why do proto-oncogenes that are expressed in many tissues become cancer causing only in some?
- Do the mechanisms that allow tissue specificity of cancer genes highlight unique features that can be exploited therapeutically for approaches that are specific for a cancer gene only in a particular cellular environment?
- Do protected or “safe” tissues that resist tumorigenesis of otherwise cancer-causing mutations contain features that can block tumour development?
Vision and Impact
The aim of this Cancer Grand Challenge is to uncover novel biological insights into the tissue specificity of cancer genes. Although it may not be feasible to develop and validate novel interventions within the timescale of a Cancer Grand Challenge, it is anticipated that proposals addressing this challenge will focus on the mechanisms with the potential to inform future approaches to prevent or treat cancer.