Toward Normalization of the Tumor Microenvironment for Cancer Therapy

The tumor microenvironment (TME) is a complex ecosystem, including blood vessels, immune cells, fibroblasts, extracellular matrix, cytokines, hormones, and so on. The TME differs from the normal tissue environment (NTE) in many aspects, such as tissue architecture, chronic inflammation, level of oxygen and pH, nutritional state of the cells, as well as tissue firmness. The NTE can inhibit the growth of cancer at the early tumorigenesis phase, whereas the TME promotes the growth of cancer in general, although it may have some anticancer effects. In particular, the TME plays a crucial role in the generation and maintenance of cancer stem cells, which lie at the root of cancer growth. Therefore, normalization of the TME to the NTE may inhibit cancer growth or improve cancer therapeutic efficiency. This review focuses on the recent emerging approaches for this normalization and the action mechanisms.