The Interplay of the Extracellular Matrix and Stromal Cells as a Drug Target in Stroma-Rich Cancers

Nina Kozlova; Joseph E. Grossman; Marcin P. Iwanicki; Taru Muranen

doi:10.1016/j.tips.2020.01.001

The Interplay of the Extracellular Matrix and Stromal Cells as a Drug Target in Stroma-Rich Cancers

Nina Kozlova, Joseph E. Grossman, Marcin P. Iwanicki, Taru Muranen

Department of Chemistry and Chemical Biology

Harvard University

Research output: Contribution to journal › Review article › peer-review

46 Scopus citations

Abstract

The tumor microenvironment (TME) is a complex neighborhood that consists of immune cells, fibroblasts, pericytes, adipocytes, endothelial and neuronal cells, and the extracellular matrix proteins. TME also consists of physical factors, such as oxygen availability, changing pH, interstitial fluid pressure, and tissue stiffness. As cancer progresses, the physical properties and the cells in the TME change significantly, impacting the efficacy of the therapies and modulating drug resistance. This has led to the development of several new treatments targeting the TME. This review focuses on recent advances on the role of TME in drug resistance, with a particular focus on the ongoing clinical trials aiming at disrupting the TME- and the extracellular matrix-mediated protection against therapies.

Original language	English
Pages (from-to)	183-198
Number of pages	16
Journal	Trends in Pharmacological Sciences
Volume	41
Issue number	3
DOIs	https://doi.org/10.1016/j.tips.2020.01.001
State	Published - Mar 2020

Keywords

cancer-associated fibroblasts
clinical trials
drug resistance
extracellular matrix
stroma-cancer crosstalk
tumor microenvironment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.tips.2020.01.001

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title = "The Interplay of the Extracellular Matrix and Stromal Cells as a Drug Target in Stroma-Rich Cancers",

abstract = "The tumor microenvironment (TME) is a complex neighborhood that consists of immune cells, fibroblasts, pericytes, adipocytes, endothelial and neuronal cells, and the extracellular matrix proteins. TME also consists of physical factors, such as oxygen availability, changing pH, interstitial fluid pressure, and tissue stiffness. As cancer progresses, the physical properties and the cells in the TME change significantly, impacting the efficacy of the therapies and modulating drug resistance. This has led to the development of several new treatments targeting the TME. This review focuses on recent advances on the role of TME in drug resistance, with a particular focus on the ongoing clinical trials aiming at disrupting the TME- and the extracellular matrix-mediated protection against therapies.",

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language = "English",

volume = "41",

pages = "183--198",

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T1 - The Interplay of the Extracellular Matrix and Stromal Cells as a Drug Target in Stroma-Rich Cancers

AU - Kozlova, Nina

AU - Grossman, Joseph E.

AU - Iwanicki, Marcin P.

AU - Muranen, Taru

PY - 2020/3

Y1 - 2020/3

N2 - The tumor microenvironment (TME) is a complex neighborhood that consists of immune cells, fibroblasts, pericytes, adipocytes, endothelial and neuronal cells, and the extracellular matrix proteins. TME also consists of physical factors, such as oxygen availability, changing pH, interstitial fluid pressure, and tissue stiffness. As cancer progresses, the physical properties and the cells in the TME change significantly, impacting the efficacy of the therapies and modulating drug resistance. This has led to the development of several new treatments targeting the TME. This review focuses on recent advances on the role of TME in drug resistance, with a particular focus on the ongoing clinical trials aiming at disrupting the TME- and the extracellular matrix-mediated protection against therapies.

AB - The tumor microenvironment (TME) is a complex neighborhood that consists of immune cells, fibroblasts, pericytes, adipocytes, endothelial and neuronal cells, and the extracellular matrix proteins. TME also consists of physical factors, such as oxygen availability, changing pH, interstitial fluid pressure, and tissue stiffness. As cancer progresses, the physical properties and the cells in the TME change significantly, impacting the efficacy of the therapies and modulating drug resistance. This has led to the development of several new treatments targeting the TME. This review focuses on recent advances on the role of TME in drug resistance, with a particular focus on the ongoing clinical trials aiming at disrupting the TME- and the extracellular matrix-mediated protection against therapies.

KW - cancer-associated fibroblasts

KW - clinical trials

KW - drug resistance

KW - extracellular matrix

KW - stroma-cancer crosstalk

KW - tumor microenvironment

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JF - Trends in Pharmacological Sciences

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The Interplay of the Extracellular Matrix and Stromal Cells as a Drug Target in Stroma-Rich Cancers

Abstract

Keywords

UN SDGs

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