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Microenvironmental regulation of tumor progression and metastasis

Abstract

Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.

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Figure 1: Multiple stromal cell types converge to support a tumorigenic primary niche.

Debbie Maizels

Figure 2: The microenvironment supports metastatic dissemination and colonization at secondary sites.

Debbie Maizels

Figure 3: Overcoming tumor dormancy and initiation of secondary outgrowth in metastatic niches.

Debbie Maizels

Figure 4: Therapeutic strategies to re-educate or target the tumor microenvironment.

Debbie Maizels

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Acknowledgements

We apologize to the many authors whose work we could not cite because of space constraints. D.F.Q. is supported by a Canadian Institutes of Health Research fellowship. Research in J.A.J.'s lab is supported by the National Cancer Institute, the American Cancer Society, the Breast Cancer Research Foundation and Cycle for Survival.

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Quail, D., Joyce, J. Microenvironmental regulation of tumor progression and metastasis. Nat Med 19, 1423–1437 (2013). https://doi.org/10.1038/nm.3394

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