Journal of Mammary Gland Biology and Neoplasia

, Volume 13, Issue 1, pp 147–156

From Bench to Bedside: Future Potential for the Translation of Prolactin Inhibitors as Breast Cancer Therapeutics

  • Charles V. Clevenger
  • Jiamao Zheng
  • Elizabeth M. Jablonski
  • Traci L. Galbaugh
  • Feng Fang
Article

DOI: 10.1007/s10911-008-9074-8

Cite this article as:
Clevenger, C.V., Zheng, J., Jablonski, E.M. et al. J Mammary Gland Biol Neoplasia (2008) 13: 147. doi:10.1007/s10911-008-9074-8

Abstract

A role for prolactin (PRL) in the pathogenesis of breast cancer has been confirmed at the cellular level in vitro, with multiple transgenic and knockout models in vivo, and within sizable patient populations through epidemiologic analysis. It is the obvious “next step” that these findings are translated into meaningful therapies to block PRL/PRLr function in human breast cancer. Several broad categories of PRL/PRLr antagonists are discussed in their pre-clinical context, including inhibitors of endocrine PRL elaboration, mutant ligand antagonists, ligand chimeras, and inhibitors of PRL-induced signaling and transactivation. The clinical potential for GHr antagonists are also discussed. These varied approaches all have demonstrated as proof-of-principle that PRL/PRLr antagonism can inhibit the in vitro and in vivo growth of breast cancer. Further pre-clinical development is required for most, however, before translation to clinical trials in breast cancer patients can occur.

Keywords

Breast cancer Prolactin receptor Pre-clinical testing Clinical trials 

Abbreviations

PRL

prolactin

PRLr

prolactin receptor

GH

growth hormone

GHr

growth hormone receptor

h

human

TGF

transforming growth factor

Wt

wild type

PPI

peptidyl prolyl isomerase

ER

estrogen receptor

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Charles V. Clevenger
    • 1
  • Jiamao Zheng
    • 2
  • Elizabeth M. Jablonski
    • 2
  • Traci L. Galbaugh
    • 2
  • Feng Fang
    • 2
  1. 1.Diana, Princess of Wales Professor of Cancer Research, Robert H. Lurie Comprehensive Cancer Center, Department of PathologyNorthwestern UniversityChicagoUSA
  2. 2.Department of PathologyNorthwestern UniversityChicagoUSA