While progress has been made in treating primary epithelial
tumors, metastatic
tumors remain largely incurable and still account for 85-90 % of all
cancer-related deaths.
Interleukin-4 (
IL4), a Th2
cytokine, and the
IL4/
IL4 receptor (IL4R) interaction have well defined roles in the immune system. Yet,
IL4 receptors are over-expressed by many epithelial
cancers and could be a promising target for metastatic
tumor therapy. The
IL4/IL4R signaling axis is a strong promoter of pro-metastatic phenotypes in epithelial
cancer cells including enhanced migration, invasion, survival, and proliferation. The promotion of
breast cancer growth specifically is also supported in part by IL4-induced
glutamine metabolism, and we have shown that
IL4 is also capable of inducing
glucose metabolism in
breast cancer cells. Importantly, there are several types of FDA approved medications for use in
asthma patients that inhibit the
IL4/IL4R signaling axis. However, these approved medications inhibit both the type I
IL4 receptor found on immune cells, and the type II
IL4 receptor that is predominantly expressed by some non-hematopoietic cells including epithelial
cancer cells. This article reviews existing
therapies targeting
IL4, IL4R, or
IL4/IL4R signaling, and recent findings guiding the creation of novel
therapies that specifically inhibit the type II IL4R, while taking into consideration effects on immune cells within the tumor microenvironment. Some of these
therapies are currently in clinical trials for
cancer patients, and may be exploitable for the treatment of metastatic disease.