Lawrence Berkeley National Laboratory

Key PointsOrgans of future metastasis are selectively and actively modified by the primary tumour before metastatic spread has occurred.Tumours induce the formation of microenvironments in distant organs that are conducive to the survival and outgrowth of tumour cells before their arrival at these sites. These microenvironments are termed pre-metastatic niches (PMNs).PMN formation is a stepwise process resulting from the combined systemic effects of tumour-secreted factors and tumour-shed extracellular vesicles.PMN formation is initiated with local changes such as the induction of vascular leakiness, remodelling of stroma and extracellular matrix, followed by systemic effects on the immune system.The development of new technologies and approaches to identify PMNs in distant organ sites in patients could revolutionize cancer treatment and lead to pre-emptive treatments to hinder metastasis.The PMN is a new paradigm for the initiation of metastasis. Our ability to fight metastasis would benefit greatly from understanding the pathological processes occurring before the development of macrometastases.