Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

David M Roy,1 Logan A Walsh21Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY, USA; 2Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: The extracellular matrix (ECM) is the complex network of proteins...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Roy DM, Walsh LA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4a2dce6037074d9e9b7cd232e3f81e4a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4a2dce6037074d9e9b7cd232e3f81e4a
record_format	dspace
spelling	oai:doaj.org-article:4a2dce6037074d9e9b7cd232e3f81e4a2021-12-02T06:49:34ZCandidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors1179-1314https://doaj.org/article/4a2dce6037074d9e9b7cd232e3f81e4a2014-07-01T00:00:00Zhttp://www.dovepress.com/candidate-prognostic-markers-in-breast-cancer-focus-on-extracellular-p-a17461https://doaj.org/toc/1179-1314 David M Roy,1 Logan A Walsh21Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY, USA; 2Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease.Keywords: uPA, RECK, ADAMs, MMPs, TIMPs, ECMRoy DMWalsh LADove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2014, Iss default, Pp 81-91 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Roy DM Walsh LA Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
description	David M Roy,1 Logan A Walsh21Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY, USA; 2Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease.Keywords: uPA, RECK, ADAMs, MMPs, TIMPs, ECM
format	article
author	Roy DM Walsh LA
author_facet	Roy DM Walsh LA
author_sort	Roy DM
title	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_short	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_full	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_fullStr	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_full_unstemmed	Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
title_sort	candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/4a2dce6037074d9e9b7cd232e3f81e4a
work_keys_str_mv	AT roydm candidateprognosticmarkersinbreastcancerfocusonextracellularproteasesandtheirinhibitors AT walshla candidateprognosticmarkersinbreastcancerfocusonextracellularproteasesandtheirinhibitors
_version_	1718399689771974656

Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

Ejemplares similares