Systemic health impact of cancer-associated extracellular vesicles and particles

Cancer is a systemic disease that perturbs the homeostasis of host tissues and organs, exerting manifestations both locally and distantly. Extracellular vesicles and particles (EVPs) have a pivotal role in intercellular communication between tumours and the host by transferring bioactive cargo to recipient cells, contributing to the systemic effects of cancer. Tumour-derived EVPs prepare distant organs for future metastasis, by creating a pre-metastatic niche (PMN). Additionally, tumours manipulate multiple organ systems to support their growth and evade immune detection. This co-option of host systems leads to cascading dysfunction across multiple organs, ultimately compromising host survival. Here we review the diverse systemic impact of cancer-associated EVPs, including immune dysregulation in PMNs, thrombosis and cardiovascular disease, liver metabolic dysfunction, glucose metabolism disorders, cachexia, and paraneoplastic syndromes of the nervous system. Furthermore, we discuss the intricate communication between host-, diet- and microbiota-derived EVPs and cancer cells, highlighting the complex interplay mediated by these EVPs in cancer progression and anti-cancer treatment responses. We also explore the prospects of EVPs as a systemic therapeutic approach for anti-cancer treatment. Overall, this Review highlights the need to address the systemic effects of cancer and to adopt holistic approaches to cancer treatment, by simultaneously targeting the tumour and its multi-organ paraneoplastic effects. These strategies hold great promise in mitigating the broad impact of disease progression and comorbidities and ultimately improving the quality of life and survival of patients.