Metastatic cancers are often resistant to conventional chemotherapy and radiotherapy, reflecting an unmet need for novel therapeutic approaches to inhibit metastasis. Growing evidence highlights the importance of targeting not only the tumour but also its ‘normal’ microenvironment – the milieu which surrounds the tumour, including stromal fibroblasts, infiltrating immune cells, blood vessels, signalling molecules, extracellular matrix and tissue oxygen. The microenvironment varies between different organs, presumably explaining the propensity of certain cancers to spread to particular sites. This review summarises current and emerging therapies targeting the metastatic microenvironment in human tumours. The role of the tumour microenvironment in the establishment and support of metastatic disease is increasingly evident. Novel therapeutic strategies targeting the microenvironment encompassing the complex interactions between tumour cells and surrounds now need to be incorporated into clinical trials with appropriate biomarker endpoints.
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