Tumor-stroma crosstalk: Targeting stroma in breast cancer

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Abstract

Purpose of review: Combinatorial strategies in cancer medicine will not only target cancer cell-intrinsic pathways, but also cancer cell-extrinsic cells, pathways, and mediators of the tumor microenvironment. The aim of the present review is to define the roles of the tumor microenvironment in primary and metastatic breast cancer progression. Recent findings: The cancer microenvironment is composed of nontransformed host stromal cells, such as endothelial cells, fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The stromal constituents contribute to the core and emergent hallmarks of cancer. In particular, they can boost sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. Summary: The stromal cells play a role in enabling or enhancing multiple hallmark capabilities in tumor microenvironment. This is a background for therapeutic-targeting strategies aimed to abrogate the stroma's contribution. Targeting tumor-associated fibroblasts, macrophages, angiogenesis and enhancing immune response may represent a paradigm-shifting approach to treating human cancer in the near future.

Original languageEnglish
Pages (from-to)551-555
Number of pages5
JournalCurrent Opinion in Oncology
Volume26
Issue number6
DOIs
Publication statusPublished - 2014

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Tumor Microenvironment
Breast Neoplasms
Neoplasms
Stromal Cells
Energy Metabolism
Extracellular Matrix
Cell Death
Endothelial Cells
Fibroblasts
Macrophages
Medicine
Neoplasm Metastasis
Growth
Therapeutics

Keywords

  • Breast cancer
  • Microenvironment
  • Tumor stroma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

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title = "Tumor-stroma crosstalk: Targeting stroma in breast cancer",
abstract = "Purpose of review: Combinatorial strategies in cancer medicine will not only target cancer cell-intrinsic pathways, but also cancer cell-extrinsic cells, pathways, and mediators of the tumor microenvironment. The aim of the present review is to define the roles of the tumor microenvironment in primary and metastatic breast cancer progression. Recent findings: The cancer microenvironment is composed of nontransformed host stromal cells, such as endothelial cells, fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The stromal constituents contribute to the core and emergent hallmarks of cancer. In particular, they can boost sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. Summary: The stromal cells play a role in enabling or enhancing multiple hallmark capabilities in tumor microenvironment. This is a background for therapeutic-targeting strategies aimed to abrogate the stroma's contribution. Targeting tumor-associated fibroblasts, macrophages, angiogenesis and enhancing immune response may represent a paradigm-shifting approach to treating human cancer in the near future.",
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N2 - Purpose of review: Combinatorial strategies in cancer medicine will not only target cancer cell-intrinsic pathways, but also cancer cell-extrinsic cells, pathways, and mediators of the tumor microenvironment. The aim of the present review is to define the roles of the tumor microenvironment in primary and metastatic breast cancer progression. Recent findings: The cancer microenvironment is composed of nontransformed host stromal cells, such as endothelial cells, fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The stromal constituents contribute to the core and emergent hallmarks of cancer. In particular, they can boost sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. Summary: The stromal cells play a role in enabling or enhancing multiple hallmark capabilities in tumor microenvironment. This is a background for therapeutic-targeting strategies aimed to abrogate the stroma's contribution. Targeting tumor-associated fibroblasts, macrophages, angiogenesis and enhancing immune response may represent a paradigm-shifting approach to treating human cancer in the near future.

AB - Purpose of review: Combinatorial strategies in cancer medicine will not only target cancer cell-intrinsic pathways, but also cancer cell-extrinsic cells, pathways, and mediators of the tumor microenvironment. The aim of the present review is to define the roles of the tumor microenvironment in primary and metastatic breast cancer progression. Recent findings: The cancer microenvironment is composed of nontransformed host stromal cells, such as endothelial cells, fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The stromal constituents contribute to the core and emergent hallmarks of cancer. In particular, they can boost sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. Summary: The stromal cells play a role in enabling or enhancing multiple hallmark capabilities in tumor microenvironment. This is a background for therapeutic-targeting strategies aimed to abrogate the stroma's contribution. Targeting tumor-associated fibroblasts, macrophages, angiogenesis and enhancing immune response may represent a paradigm-shifting approach to treating human cancer in the near future.

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