The extracellular matrix (ECM) is a dynamic meshwork of proteins and glycans that provides architectural support to cells and transmits mechanical and biochemical cues. In cancer, remodelling of the ECM — in composition, architecture and mechanical properties — is a hallmark that correlates with tumour aggressiveness and patient survival. Because the ECM is abundant and relatively accessible, it is an attractive source of potential biomarkers and therapeutic targets.
The ECM comprises a wide array of proteins and glycans whose collective composition and arrangement form the tumour matrisome. This meshwork not only gives structural support but also conveys signals that regulate core cellular behaviours such as proliferation, survival and migration. ECM accumulation and desmoplastic remodelling have long been associated with prognosis in multiple tumour types; classical pathology and clinical studies have linked fibrosis or desmoplasia with disease course.
Over recent years, development of novel proteomic and imaging methods has transformed the capacity to define ECM composition, physical and mechanical properties, and signalling functions. These technologies enable more precise description of the tumour matrisome and its heterogeneity across cancers. Improved analytical approaches provide opportunities to identify tumour-specific ECM proteins and to characterise ECM architecture and mechanics that can influence cell behaviour and treatment response.
The tumour ECM modulates functions of all cell populations within the tumour microenvironment via biochemical ligands, mechanical cues and architecture. ECM components and remodelling enzymes influence cell–matrix adhesion, matrix stiffness and the availability of matricryptic signals, thereby affecting hallmarks of cancer such as invasion, immune modulation and therapy resistance. Matrix metalloproteinases and other ECM-remodelling factors have been recognised as central regulators of tumour microenvironmental dynamics.
Given its abundance and tumour-associated remodelling, the ECM can be exploited for diagnostic and prognostic applications. Tumour-specific ECM proteins or signatures hold promise as anchors for imaging agents or as circulating or tissue biomarkers in prognostic tests. Advances in proteomics and imaging facilitate identification of ECM features that correlate with clinical outcomes, supporting the development of ECM-informed diagnostic strategies.
Several conceptual and practical strategies are being pursued to harness the tumour ECM for therapeutic benefit:
Targeted delivery: Tumour-specific ECM proteins can serve as anchoring sites for the targeted delivery of imaging agents or therapeutic payloads, increasing localisation to tumour tissue.
Matritherapies: Approaches that aim to normalise the architecture and mechanical properties of the tumour ECM — termed matritherapies — seek to reverse detrimental ECM remodelling and restore a microenvironment less permissive to tumour progression.
Signalling modulation: Targeting interactions between ECM proteins and their receptors, or intervening in downstream signalling cascades, represents another route to alter tumour cell behaviour influenced by the ECM.
These strategies build on the improved molecular and biophysical characterisation of the matrisome and on identification of tumour-restricted ECM components.
Early clinical attempts to target the ECM in cancer patients did not yield clear clinical benefit. Examples cited in the literature include efforts to inhibit matrix metalloproteinases and to target integrins; these past failures highlight the complexity of ECM biology and the challenge of safely modulating ECM functions in patients. The source emphasises that advances in basic ECM biology, together with new proteomic and imaging technologies, are changing the landscape and may enable more rational, effective translation of ECM-targeting strategies.
Careful selection of ECM targets, reliable characterisation of tumour-specific matrisome features, and strategies that consider the ECM’s multifaceted roles are required to improve the likelihood of clinical success.
The tumour matrisome is both a mechanistic contributor to tumour progression and an accessible resource for biomarkers and therapeutic targeting. Novel technologies now allow deeper interrogation of ECM composition, mechanics and signalling, and these insights are guiding strategies to exploit the ECM for diagnostics and therapy. Approaches such as targeted delivery to tumour-specific ECM proteins, matritherapies to normalise ECM architecture, and modulation of ECM–receptor signalling offer promising avenues. However, the history of unsuccessful early interventions underlines the need for rigorous, biology-informed development and clinical evaluation. The source provides figures summarising ECM roles, properties, signalling pathways, diagnostic leveraging and therapeutic strategies, and references foundational and recent literature on ECM composition, remodelling enzymes and clinical attempts to target ECM components.