Neurokinin Receptors as Potential Targets in Breast Cancer Treatment

Pranela      Rameshwar; Bobby   Y.   Reddy; Katarzyna   A.   Trzaska; Raghav   G.   Murthy; Peter      Navarro

Abstract

Despite recent advances in the diagnoses and treatment of breast cancer, this disease continues to be a major cause of death. One of the biggest challenges in breast cancer treatment is bone metastasis. Breast cancer cells (BCCs) are capable of migrating to the bone marrow and utilizing the marrow microenvironment to remain quiescent. While exhibiting quiescence in the marrow, BCCs can evade the effects of conventional cancer treatments such as chemotherapy. Therefore, scientists must find a new paradigm to target these quiescent BCCs. The development of potential targets may require a more comprehensive understanding of the marrow microenvironment and its regulators. The preprotachykinin-1 (PPT-I) gene encodes for the tachykinin peptides, which interact with neurokinin (NK) receptors. Studies have correlated this interaction with BCC integration into the bone marrow and breast cancer progression. In this review, we discuss the roles that different factors of the marrow microenvironment play in breast cancer and targets of NK receptors as potential treatment options.

Keywords: Neurokinin receptor, breast cancer, tachykinins, CXCR4, SDF-1α, bone marrow, substance P, preprotachykinin-I