A survey of herbal medicines as tumor microenvironment-modulating agents

The tumor microenvironment (TME) is extremely complex, involving extensive interactions among stromal cells, immune cells, and signaling molecules. Therefore, an approach targeting the TME has emerged as a promising therapeutic strategy. Herbal medicines consist of multiple active compounds, which have multi-target effects. Therefore, they have been regarded as potential anticancer agents; multiple studies have explored their effects on the TME. In this review, we report the effects of 29 single herb medicines or herbal formulas on the TME, based on the findings of 64 published studies. Specifically, we describe the effects of these herbal medicines on cancer-associated fibroblasts/tumor-associated fibroblasts, tumor-associated endothelial cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Among the reviewed herbal medicines, the most promising TME-modulating effects were exhibited by curcumin, DHA, EGCG, resveratrol, and silibinin; these medicines showed the ability to regulate two or more components of the TME. The findings of this review support the notion that the combination of herbal medicines with conventional anticancer therapies are likely to exhibit a clinical benefit, which should be further explored in clinical trials.