Remodeling the Irradiated Tumor Microenvironment: The Fifth R of Radiobiology?
Remodeling the Irradiated Tumor Microenvironment: The Fifth R of Radiobiology?
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DOI：
10.1007/978-3-319-40854-5_6
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发表时间：
2017-01-01
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影响因子：
--
通讯作者：
Barcellos-Hoff, Mary Helen
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文献类型：
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作者：
Barcellos-Hoff, Mary Helen
With the recognition that the host and tumor are inextricably intertwined as a malignant system, the tumor microenvironment (TME) is now considered to be an important target in cancer therapy. A long-standing objective to improve the therapeutic ratio of radiotherapy has been to manipulate microenvironmental factors that impede cancer cell radiosensitivity, most notably hypoxia. A more recent idea is to eradicate or reeducate the components of TME that support and sustain cancer in order to better control the local tumor and prevent metastatic disease. The TME includes the vasculature, stromal cells, and immune cells, each of which is locally corrupted by the presence of cancer, which itself influences distant tissue and cell behaviors. The biology of the irradiated TME provides robust targets to augment local tumor control and intersect with immunological mechanisms that can eliminate distant disease. Transforming growth factor beta (TGF beta) is an example of a critical mediator of the irradiated TME. TGF beta inhibition in the context of radiotherapy is predicated on understanding its mechanistic opposition to therapeutic benefit. Therapeutic strategies to biologically augment radiotherapy by preventing the reestablishment of a functional TME could motivate the addition to the classic "Rs" of radiation biology in oncology: repair, reoxygenation, repopulation, redistribution, and now, remodeling the TME.
