---
title: "Targeting the tumour matrisome: advances in ECM biology, diagnostics and therapies"
id: "nature-reviews-clinical-oncology-0-understanding-and-targeting-the-tumour-matrisome"
canonical_url: "https://medichelpline.com/clinical-feed/nature-reviews-clinical-oncology-0-understanding-and-targeting-the-tumour-matrisome"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "Nature Reviews Clinical Oncology"
source_url: "https://www.nature.com/articles/s41571-026-01203-5"
published_at: "2026-09-21T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Targeting the tumour matrisome: advances in ECM biology, diagnostics and therapies
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/nature-reviews-clinical-oncology-0-understanding-and-targeting-the-tumour-matrisome
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** Nature Reviews Clinical Oncology
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41571-026-01203-5)
- **Published At:** 2026-09-21T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The **extracellular matrix (ECM)** is a dynamic meshwork of proteins and glycans that provides structural support and transmits mechanical and biochemical signals regulating proliferation, survival and migration. - ECM accumulation and remodelling of composition, architecture and mechanics are hallmarks of cancer and correlate with tumour aggressiveness and patient survival across cancer types. - The tumour ECM can modulate the functions of all cell populations in the tumour microenvironment and thereby influence multiple cancer hallmarks. - Early clinical attempts to target the ECM, including matrix metalloproteinase inhibitors and integrin-targeting agents, failed to show clinical benefit in patients; details of specific trial outcomes are noted in referenced literature but were not fully reported in this source preview. - Recent advances in proteomic and imaging technologies have substantially improved the ability to define ECM composition, physical and mechanical properties, and signalling functions. - The **ECM** is an accessible reservoir of potential biomarkers; tumour-specific ECM components can be used for prognostic or diagnostic tests and as anchors for targeted delivery of imaging or therapeutic payloads. - Therapeutic approaches under consideration include using tumour-specific ECM proteins for targeted delivery, normalizing ECM architecture and mechanics through **matritherapies**, and modulating ECM–receptor interactions or downstream signalling cascades. - Leveraging the tumour ECM for clinical benefit requires integrating improved fundamental understanding of ECM biology with novel technologies to measure and manipulate ECM properties. - Figures in the source summarize: the role of the ECM in cancer; ECM architectural, mechanical and biochemical properties; ECM-dependent signalling pathways; strategies to leverage the ECM for diagnostics/prognostics; and approaches to target the tumour ECM for therapeutic benefit. - Overall, the tumour matrisome represents both a mechanistic driver of tumour progression and a promising, yet challenging, target for diagnostics and therapy.
## Clinical Analysis & Structured Key Points
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[nature](https://www.nature.com/) 2. [nature reviews clinical oncology](https://www.nature.com/nrclinonc) 3. [review articles](https://www.nature.com/nrclinonc/articles?type=review-article) 4. article * Review Article * Published: 21 September 2026 # Understanding and targeting the tumour matrisome * [Dharma Pally](https://www.nature.com/articles/s41571-026-01203-5#auth-Dharma-Pally-Aff1)[1](https://www.nature.com/articles/s41571-026-01203-5#Aff1) [na1](https://www.nature.com/articles/s41571-026-01203-5#na1), * [Johanna I. Englund](https://www.nature.com/articles/s41571-026-01203-5#auth-Johanna_I_-Englund-Aff2) [ORCID: orcid.org/0000-0001-9637-6843](https://orcid.org/0000-0001-9637-6843)[2](https://www.nature.com/articles/s41571-026-01203-5#Aff2) [na1](https://www.nature.com/articles/s41571-026-01203-5#na1) & * [Alexandra Naba](https://www.nature.com/articles/s41571-026-01203-5#auth-Alexandra-Naba-Aff1-Aff3) [ORCID: orcid.org/0000-0002-4796-5614](https://orcid.org/0000-0002-4796-5614)[1](https://www.nature.com/articles/s41571-026-01203-5#Aff1),[3](https://www.nature.com/articles/s41571-026-01203-5#Aff3) [_Nature Reviews Clinical Oncology_](https://www.nature.com/nrclinonc) (2026) [Cite this article](https://www.nature.com/articles/s41571-026-01203-5#citeas) [ Save article ](https://www.nature.com/articles/s41571-026-01203-5/save-research?_csrf=prsob2NXaRwFE8zIdIp77HJcjRhcToT9) [ View saved research ](https://www.nature.com/saved-research) ## Abstract 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. ## Key points * The extracellular matrix (ECM) is an abundant component of the tumour microenvironment with the potential to modulate the functions of all cell populations of the tumour microenvironment. * Remodelling of the composition, architecture and mechanical properties of the ECM is a hallmark of cancer. * The composition and properties of the ECM can be leveraged for diagnostic and/or prognostic testing. * Tumour-specific ECM proteins can serve as anchors for the targeted delivery of imaging or therapeutic agents to tumours. * ‘Matritherapies’ offer opportunities to normalize the architecture and mechanical properties of the tumour ECM to achieve therapeutic benefit. * Targeting the interactions between ECM proteins and their receptors, or the downstream signalling cascades they trigger, might offer novel therapeutic opportunities. This is a preview of subscription content, [access via your institution](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41571-026-01203-5) ## Access options [ Access through your institution ](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41571-026-01203-5) Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription 27,99 € / 30 days cancel any time [Learn more](https://shop.nature.com/products/plus/?region=ROW) Subscribe to this journal Receive 12 print issues and online access 176,64 € per year only 14,72 € per issue [Learn more](https://www.nature.com/nrclinonc/subscribe) Buy this article * Purchase on SpringerLink * Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout ### Additional access options: * [Log in](https://idp.nature.com/authorize/natureuser?client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41571-026-01203-5) * [Learn about institutional subscriptions](https://www.springernature.com/gp/librarians/licensing/license-options) * [Read our FAQs](https://support.nature.com/en/support/home) * [Contact customer support](https://www.springernature.com/gp/contact) **Fig. 1: The role of the ECM in cancer.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41571-026-01203-5/MediaObjects/41571_2026_1203_Fig1_HTML.png) **Fig. 2: Architectural, mechanical and biochemical properties of the ECM.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41571-026-01203-5/MediaObjects/41571_2026_1203_Fig2_HTML.png) **Fig. 3: ECM-dependent signalling pathways modulating the hallmarks of cancer.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41571-026-01203-5/MediaObjects/41571_2026_1203_Fig3_HTML.png) **Fig. 4: Leveraging the tumour ECM for prognostic and diagnostic purposes.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41571-026-01203-5/MediaObjects/41571_2026_1203_Fig4_HTML.png) **Fig. 5: Targeting the tumour ECM to achieve therapeutic benefits.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41571-026-01203-5/MediaObjects/41571_2026_1203_Fig5_HTML.png) ### Explore related subjects Discover the latest articles and news in related subjects. * [Cancer microenvironment](https://www.nature.com/subjects/cancer-microenvironment) * [Drug development](https://www.nature.com/subjects/drug-development) * [Prognostic markers](https://www.nature.com/subjects/prognostic-markers) * [Tumour biomarkers](https://www.nature.com/subjects/tumour-biomarkers) ## References 1. 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