Role of the extracellular matrix in cancer: insights into tumor progression and therapy

The extracellular matrix (ECM) serves not only as a structural scaffold but also as an active regulator of cancer progression, profoundly influencing tumor behaviour and the tumor microenvironment (TME). This review focuses into the pivotal role of ECM alterations in facilitating tumor metastasis and explores therapeutic strategies aimed at counteracting these changes. We analyse targeted interventions against collagen, including approaches to inhibit its biosynthesis and disrupt associated signalling pathways critical for tumor architecture and cell migration. Additionally, therapies addressing hyaluronan are reviewed, highlighting methods to suppress its synthesis and enzymatic strategies to degrade it, thereby mitigating its tumor-promoting effects. The discussion extends to innovative approaches for modulating ECM stiffness, focusing on the roles of cancer-associated fibroblasts and lysyl oxidases, which are key contributors to ECM remodelling and mechanical signalling. By strategically modifying these ECM components, these interventions aim to enhance the efficacy of existing cancer treatments, tackle resistance mechanisms, and achieve more durable therapeutic outcomes. Insights from recent studies and clinical trials highlight the promise of these strategies in overcoming treatment resistance and improving patient outcomes. Advancing our understanding of ECM biology leads to the development of innovative and more effective cancer therapies.