Role of IL-17/IL-17R axis in regulating breast tumorigenesis

Inflammation is a normal response by the body to any environmental insult such as tissue injury or invading bacteria. Tightly controlled inflammation is necessary for wound healing and effective elimination of the invading pathogen without causing severe unwanted tissue damage. However, uncontrolled inflammation can be troublesome. There is an abundance of evidence showing a strong linkage between inflammation and increased risks of developing certain cancers, including breast cancer. Thus, targeting the process of inflammation is an attractive new intervention strategy for combating breast cancer. However, because inflammation is a very complex process that involves numerous soluble molecules and many different cell types, identification of dominant molecular pathways that are responsible for inflammation-related tumor growth is a key step for developing such new therapies. We have obtained preliminary evidence supporting a dominant role of the molecular pathway mediated by pro-inflammatory cytokines IL-17A, IL-17F and their cognate receptors IL-17RA and IL-17RC. In this application, we propose to use mouse models of breast cancer to confirm our initial observations and to understand why and how the IL-17/IL-17 receptor pathway is involved in promoting tumor growth and metastasis. The knowledge that we intend to obtain from this study is critically required before our IL-17 receptor antagonist therapy can be moved into human clinical trials.