GPR161 RECEPTOR AS A NOVEL TARGET FOR ANTIBODY-BASED IMMUNOTHERAPY OF TRIPLE-NEGATIVE BREAST CANCER

Abstract

Triple-negative breast cancer is a rare type of breast cancer, accounting for 20% of all women diagnosed with the adenocarcinoma. Triple-negative breast cancer cells are mainly characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptors. Moreover, these cells do not respond to hormonal and targeted treatment with monoclonal antibodies. A literature review revealed several receptors in the oncogenic cells of this phenotype with potential to serve as a novel target for therapy. In particular, the G-protein coupled receptor (GPR) 161 was found to be overexpressed in triple-negative breast cancer cells, and correlated with a poor prognosis of the disease. In addition, overexpression of GPR161 in human mammary epithelial cells resulted in increased cell proliferation, migration, intracellular accumulation of E-cadherin, and the formation of multiple structures in a three-dimensional cell culture. Activation of the receptor reduces the phosphorylation of GTPase-activating protein 1 proteins, thereby enhancing mammalian target of rapamycin signaling pathways.
 GPCRs belong to a family of cell membrane proteins that transform extracellular signals into intracellular signaling pathways. These receptors play a key role in many important physiological processes whose malfunction may lead to various diseases, including cancer. Several currently produced drugs target different members of the GPCR family and have shown excellent therapeutic advantages.
 Therefore, huge efforts are focused on developing new drugs based on GPCRs, particularly for the treatment of cancer. This article provides an overview of data that show great promise in new opportunities for the treatment of triple-negative breast cancer. In particular, research on GPCRs is highlighted as promising targets for monoclonal antibodies and, after humanization, as therapeutic drugs