Gut feeling: extracellular vesicles dictate liver’s susceptibility to colorectal cancer metastasis

Colorectal cancer (CRC) represents a major global health issue, ranking as the third most common tumour and the second leading cause of cancer-related mortality worldwide.1 Distant metastasis is the primary cause of fatality for patients with cancer. CRC often presents as metastatic disease at diagnosis, and up to 70% of patients who undergo curative surgery of the primary tumour will eventually develop metastases. The liver is the most common site for CRC metastatic spread. Despite significant progress in surgical interventions and treatments, a large number of patients with CRC have inoperable liver metastases or experience recurrence after surgery. To develop new therapeutic strategies and improve the management of advanced CRC, a deep understanding of the metastatic process is of utmost importance. In recent decades, we have learnt that the tumour microenvironment (TME) plays a central role in every phase of oncogenesis and tumour development. The reciprocal and dynamic communication between cancer cells and resident cells, via both paracrine and physical interactions, determines the clinical behaviour of cancer and can affect patients’ response to therapy to a similar extent as the mutational burden leading to oncogenic pathway activation. The liver stands out as a unique and complex microenvironment, distinctly characterised by its tolerogenic nature. This prevents undesirable and excessive immune responses to the high volume of harmless antigens conveyed …