Systemic responses

Cancer is associated with widespread systemic perturbations such as inflammation that may be captured in the molecular profiles of genes, proteins, metabolites and DNA methylation in peripheral and target tissues. The Systemic Responses theme investigates these systemic perturbations to inform strategies for the early detection, precision prevention, and treatment of cancer.

Highlights include:

Cancer is associated with widespread systemic perturbations that may be captured in molecular profiles such as the proteomes, transcriptomes and methylomes of peripheral and target tissues. Inflammation, for example, is prominent in cancer, contributing to microenvironments that foster tumorigenesis and metastasis. Consequently, understanding cancer risk, progression and survival requires a deep understanding of these systemic perturbations beyond the contributions of individual genes.

Toward this goal, we systematically characterise systemic perturbations linked to cancer using multi-omic profiles at the level of molecular pathways and high-level processes, distinguishing between mere associations and causal relationships using recently-developed hypothesis-free causal inference methods.

Building on known associations between aging and inflammation on cancer risk, the Systemic responses theme aims to use these associations to discover (1) molecular biomarkers of cancer risk for risk stratification and early detection and (2) therapeutic targets for preventing and treating cancer. 

Candidate molecular markers have been selected from among those known to be associated with ageing (e.g. epigenetic clocks) and with inflammation (e.g. inflammatory proteins) in peripheral tissues. These will be integrated into models of cancer risk using machine learning algorithms using molecular data from case-control studies. These markers will in parallel be evaluated for their potential as therapeutic targets by applying Mendelian randomization to evaluate evidence for causal relationships between these markers and cancer risk.

Watch an overview by Matt Suderman, who co-chairs the Systemic responses theme with Paul Yousefi.
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