Contribution of toll-like receptor signaling pathways to breast tumorigenesis and treatment

La Creis R Kidd,^1,* Erica N Rogers,^2,* Susan T Yeyeodu,² Dominique Z Jones,¹ K Sean Kimbro<sup>2

1</sup>Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, ²Biomedical/Biotechnology Research Institute (BBRI), North Carolina Central University, Durham, NC, USA

^*These authors contributed equally to this manuscript and are co-first authors

Abstract: Mounting evidence indicates that anomalies in the inflammatory and immune response pathways are essential to tumorigenesis. However, tumor-based innate immunity initiated by transformed breast epithelia tissues has received much less attention. This review summarizes published reports on the role of the toll-like receptor signaling pathway on breast cancer risk, disease progression, survival, and disease recurrence. Specifically, we discuss the underlying biological mechanisms that contribute to the tumorigenic and/or anti-tumorigenic properties of toll-like receptors and their associated agonists in relation to breast tumorigenesis and cancer treatment. Further, we use results from preclinical, clinical, and population-based studies as prompts for the exploration of new and more effective breast cancer therapies. As the knowledge base of innate immunity's involvement in breast cancer progression increases, current and new immune-modifying strategies will be refined to effectively treat breast cancer.

Keywords: TLR, single nucleotide polymorphism, chemotherapy, radiotherapy, innate immunity