Bad company: Microenvironmentally mediated resistance to targeted therapy in melanoma

Filipe V. Almeida; Stephen M. Douglass; Mitchell E. Fane; Ashani T. Weeraratna

doi:10.1111/pcmr.12736

Bad company: Microenvironmentally mediated resistance to targeted therapy in melanoma

Filipe V. Almeida, Stephen M. Douglass, Mitchell E. Fane, Ashani T. Weeraratna

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

16 Scopus citations

Abstract

This review will focus on the role of the tumor microenvironment (TME) in the development of drug resistance in melanoma. Resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma is observed months after treatment, a phenomenon that is often attributed to the incredible plasticity of melanoma cells but may also depend on the TME. The TME is unique in its cellular composition—it contains fibroblasts, immune cells, endothelial cells, adipocytes, and among others. In addition, the TME provides “non-homeostatic” levels of oxygen, nutrients (hypoxia and metabolic stress), and extracellular matrix proteins, creating a pro-tumorigenic niche that drives resistance to MAPKi treatment. In this review, we will focus on how changes in the tumor microenvironment regulate MAPKi resistance.

Original language	English (US)
Pages (from-to)	237-247
Number of pages	11
Journal	Pigment Cell and Melanoma Research
Volume	32
Issue number	2
DOIs	https://doi.org/10.1111/pcmr.12736
State	Published - Mar 1 2019
Externally published	Yes

Keywords

drug resistance
hypoxia
immunology
mechanotransduction
melanoma
oxidative stress

ASJC Scopus subject areas

Oncology
General Biochemistry, Genetics and Molecular Biology
Dermatology

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10.1111/pcmr.12736

Cite this

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title = "Bad company: Microenvironmentally mediated resistance to targeted therapy in melanoma",

abstract = "This review will focus on the role of the tumor microenvironment (TME) in the development of drug resistance in melanoma. Resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma is observed months after treatment, a phenomenon that is often attributed to the incredible plasticity of melanoma cells but may also depend on the TME. The TME is unique in its cellular composition—it contains fibroblasts, immune cells, endothelial cells, adipocytes, and among others. In addition, the TME provides “non-homeostatic” levels of oxygen, nutrients (hypoxia and metabolic stress), and extracellular matrix proteins, creating a pro-tumorigenic niche that drives resistance to MAPKi treatment. In this review, we will focus on how changes in the tumor microenvironment regulate MAPKi resistance.",

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author = "Almeida, {Filipe V.} and Douglass, {Stephen M.} and Fane, {Mitchell E.} and Weeraratna, {Ashani T.}",

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T2 - Microenvironmentally mediated resistance to targeted therapy in melanoma

AU - Almeida, Filipe V.

AU - Douglass, Stephen M.

AU - Fane, Mitchell E.

AU - Weeraratna, Ashani T.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - This review will focus on the role of the tumor microenvironment (TME) in the development of drug resistance in melanoma. Resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma is observed months after treatment, a phenomenon that is often attributed to the incredible plasticity of melanoma cells but may also depend on the TME. The TME is unique in its cellular composition—it contains fibroblasts, immune cells, endothelial cells, adipocytes, and among others. In addition, the TME provides “non-homeostatic” levels of oxygen, nutrients (hypoxia and metabolic stress), and extracellular matrix proteins, creating a pro-tumorigenic niche that drives resistance to MAPKi treatment. In this review, we will focus on how changes in the tumor microenvironment regulate MAPKi resistance.

AB - This review will focus on the role of the tumor microenvironment (TME) in the development of drug resistance in melanoma. Resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma is observed months after treatment, a phenomenon that is often attributed to the incredible plasticity of melanoma cells but may also depend on the TME. The TME is unique in its cellular composition—it contains fibroblasts, immune cells, endothelial cells, adipocytes, and among others. In addition, the TME provides “non-homeostatic” levels of oxygen, nutrients (hypoxia and metabolic stress), and extracellular matrix proteins, creating a pro-tumorigenic niche that drives resistance to MAPKi treatment. In this review, we will focus on how changes in the tumor microenvironment regulate MAPKi resistance.

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KW - hypoxia

KW - immunology

KW - mechanotransduction

KW - melanoma

KW - oxidative stress

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Bad company: Microenvironmentally mediated resistance to targeted therapy in melanoma

Abstract

Keywords

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