Small molecules modulating tumor-stromal cell interactions: new candidates for anti-tumor drugs.

The tumor microenvironment comprises tumor cells surrounding normal cells and the extracellular matrix. The surrounding normal cells have critical roles in the regulation of growth and metastasis of cancers, including the maintenance of cancer stem cells and the formation of cancer metastatic niches. Recent anti-tumor strategies targeting the tumor microenvironment have included inhibition of angiogenesis and the augmentation of immune reactions. However, in this review, we will focus on stromal cells (fibroblast-like cells), a common constituent of the tumor microenvironment. Since stromal cells regulate the growth of cancer cells positively and negatively through adhesion and secreted factors, anti-tumor strategies should consider modulating tumor-stromal cell interactions through use of small molecules.