Cancer Grand Challenges - InteroCANCEption - Crosstalk between cancer and the nervous system via interoception - Abstract - InteroCANCEption Our nerves do far more than make us feel pain or control movement - they constantly monitor and regulate what is happening inside our body. This hidden “internal sense”, called interoception, connects every organ to the brain through an intricate network of nerve fibres. These nerve signals help the body balance metabolism, immunity, and organ function. Notably, while the extensive connectivity of the peripheral nervous system has been described for hundreds of years, only in the last decade or so have we begun to appreciate the role of this neural network in bidirectional communication between body and brain (the so-called body- brain axis). Recent research shows that this communication between body and brain also plays a crucial role in various diseases, but we still know very little about how or why. In this project, we will explore whether our brain also uses interoception to monitor and respond to cancer. If so, could we manipulate these neural signals to adjust how the cancer grows or how the immune system fights cancer? Our research will investigate this two-way communication between tumours and the nervous system - what we call the Cancer Interoception. Using animal models that mimic different subtypes of three human cancers (pancreatic, lung, colorectal) combined with advanced tools in neuroscience, genetics, immunology, and cancer biology, we will identify which neural pathways are most affected by cancer and how different tumour types and locations shape these interactions. We expect that, much like immune responses to cancer, nerve involvement varies depending on the type and stage of the tumour. Certain neural circuits that sense and respond to cancer overlap with pathways that control local and systemic responses in other physiological and pathological conditions. We will identify these points of intersection, where cancer-related interoceptive circuits and other body–brain pathways converge, to understand how co-existing conditions influence tumour development. In particular, we will focus on inflammation, infection, and altered metabolic status, since these conditions are commonly associated with cancer progression. This project brings together neuroscience, immunology, and neurotechnology into cancer research, to tackle a major unanswered question: how does the brain perceive and influence cancer? Understanding this hidden dialogue between nerves and tumours could transform how we think about cancer biology and open up entirely new therapeutic possibilities. We will use our findings to develop novel approaches to treat cancer; such interventions could include precision drugs or small implanted devices that modify nerve activity. These devices have already been extensively applied to patients with neurological diseases; we will repurpose them for cancer therapy, offering new ways to slow tumour growth, reduce symptoms, and improve quality of life for people with cancer.
