Understanding and targeting the tumour matrisome

The extracellular matrix (ECM) is a dynamic meshwork of proteins and glycans that provides architectural support to cells. This meshwork also conveys mechanical and biochemical signals that orchestrate many cellular processes, including proliferation, survival and migration. ECM accumulation is a hallmark of cancers and correlates with tumour aggressiveness and survival across cancer types. Because of its abundance and accessibility, the ECM constitutes an appealing reservoir of potential biomarkers and therapeutic targets. Yet, early attempts to target the ECM in patients with cancer have failed to provide clinical benefit. Over the past few years, the development of novel proteomic and imaging methods, together with advances in our knowledge of ECM biology provided by fundamental research, have transformed our understanding of the roles of the ECM in tumour progression. In this Review, we describe novel technologies developed to define the composition, physical and mechanical properties, and signalling functions of the ECM and provide an overview of ECM-dependent mechanisms regulating tumour progression. We then illustrate how the ECM is being leveraged to devise prognostic or diagnostic clinical tests. Lastly, we discuss strategies to target the ECM for clinical benefit by using the ECM for the targeted delivery of therapeutic payloads, normalizing the tumour ECM through matritherapies or modulating ECM signalling pathways.