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Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors
The extracellular matrix (ECM) is a complex network composed of a multitude of different macromolecules. ECM components typically provide a supportive structure to the tissue and engender positional information and crosstalk with neighboring cells in a dynamic reciprocal manner, thereby regulating t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387567/ https://www.ncbi.nlm.nih.gov/pubmed/32793493 http://dx.doi.org/10.3389/fonc.2020.01231 |
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author | Lorusso, Girieca Rüegg, Curzio Kuonen, François |
author_facet | Lorusso, Girieca Rüegg, Curzio Kuonen, François |
author_sort | Lorusso, Girieca |
collection | PubMed |
description | The extracellular matrix (ECM) is a complex network composed of a multitude of different macromolecules. ECM components typically provide a supportive structure to the tissue and engender positional information and crosstalk with neighboring cells in a dynamic reciprocal manner, thereby regulating tissue development and homeostasis. During tumor progression, tumor cells commonly modify and hijack the surrounding ECM to sustain anchorage-dependent growth and survival, guide migration, store pro-tumorigenic cell-derived molecules and present them to enhance receptor activation. Thereby, ECM potentially supports tumor progression at various steps from initiation, to local growth, invasion, and systemic dissemination and ECM-tumor cells interactions have long been considered promising targets for cancer therapy. Integrins represent key surface receptors for the tumor cell to sense and interact with the ECM. Yet, attempts to therapeutically impinge on these interactions using integrin inhibitors have failed to deliver anticipated results, and integrin inhibitors are still missing in the emerging arsenal of drugs for targeted therapies. This paradox situation should urge the field to reconsider the role of integrins in cancer and their targeting, but also to envisage alternative strategies. Here, we review the therapeutic targets implicated in tumor cell adhesion to the ECM, whose inhibitors are currently in clinical trials and may offer alternatives to integrin inhibition. |
format | Online Article Text |
id | pubmed-7387567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73875672020-08-12 Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors Lorusso, Girieca Rüegg, Curzio Kuonen, François Front Oncol Oncology The extracellular matrix (ECM) is a complex network composed of a multitude of different macromolecules. ECM components typically provide a supportive structure to the tissue and engender positional information and crosstalk with neighboring cells in a dynamic reciprocal manner, thereby regulating tissue development and homeostasis. During tumor progression, tumor cells commonly modify and hijack the surrounding ECM to sustain anchorage-dependent growth and survival, guide migration, store pro-tumorigenic cell-derived molecules and present them to enhance receptor activation. Thereby, ECM potentially supports tumor progression at various steps from initiation, to local growth, invasion, and systemic dissemination and ECM-tumor cells interactions have long been considered promising targets for cancer therapy. Integrins represent key surface receptors for the tumor cell to sense and interact with the ECM. Yet, attempts to therapeutically impinge on these interactions using integrin inhibitors have failed to deliver anticipated results, and integrin inhibitors are still missing in the emerging arsenal of drugs for targeted therapies. This paradox situation should urge the field to reconsider the role of integrins in cancer and their targeting, but also to envisage alternative strategies. Here, we review the therapeutic targets implicated in tumor cell adhesion to the ECM, whose inhibitors are currently in clinical trials and may offer alternatives to integrin inhibition. Frontiers Media S.A. 2020-07-22 /pmc/articles/PMC7387567/ /pubmed/32793493 http://dx.doi.org/10.3389/fonc.2020.01231 Text en Copyright © 2020 Lorusso, Rüegg and Kuonen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Lorusso, Girieca Rüegg, Curzio Kuonen, François Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors |
title | Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors |
title_full | Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors |
title_fullStr | Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors |
title_full_unstemmed | Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors |
title_short | Targeting the Extra-Cellular Matrix—Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors |
title_sort | targeting the extra-cellular matrix—tumor cell crosstalk for anti-cancer therapy: emerging alternatives to integrin inhibitors |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387567/ https://www.ncbi.nlm.nih.gov/pubmed/32793493 http://dx.doi.org/10.3389/fonc.2020.01231 |
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