Small Molecule Inhibitors of the Prolactin Receptor in Breast Cancer

摘要

Breast cancer is both a common and a significant health concern for women across the globe. Emerging evidence suggests that the prolactin (PRL) signaling cascade contributes to the pathophysiology of breast cancer as well as to chemoresistance. The importance of this pathway to breast cancer has been elucidated by in vitro studies, genetic manipulations in mice, and case control analyses in human populations. To date, a number of different strategies, none of which have yet made it to the clinical stage, have been advanced as a means for blocking the PRL receptor (PRLR). This paper presents the rationale and strategy for the development of novel small molecule competitive antagonists of the PRLR as a therapeutics in breast cancer. It is predicted that the future of breast cancer treatment will continue to evolve and will be different than what it is today. Combination therapies will be applied that will concurrently target multiple molecules of interest. Novel small molecules will be employed as a means to turn off the PRL signaling pathway in breast cancer cells. Different molecules may well be applied to different genotypic individuals on the basis of the polymorphism profile that their PRLR harbors.