Pharmacological modulation of IGF serum concentrations as a therapeutic approach to control the growth of malignant breast tumors

The insulin-like growth factors (IGFs)-1 and -2 have been associated with an increased risk for breast cancer, and have been shown to increase tumor growth and malignant behavior in vitro and in vivo. Both exert their actions through the IGF type 1 receptor (IGF1R), which is able to cooperate with the estrogen receptor in the regulation of growth-associated gene expression. The inhibition of IGF1R signaling, either through receptor blocking or through a reduction of bioactive ligands thus appears to be a highly desirable goal in the suppression of tumor growth. This paper presents a number of compounds that have been shown to reduce IGF serum levels and that might therefore have a potential in controlling tumor growth and possibly metastatic behavior. Some of these are believed to work through a reduction of systemic estrogens, such as anti-estrogens, selective estrogen receptor mediators and aromatase inhibitors, others represent synthetic compounds that belong to the vitamin A and D family.