Damiano, Jason and Wasserman, Ernesto (2013) Molecular Pathways: Blockade of the PRLR Signaling Pathway as a Novel Anti-hormonal Approach for the Treatment of Breast and Prostate Cancer. Clinical Cancer Research. ISSN 1078-0432

Abstract

The prolactin (PRL)–prolactin receptor (PRLR) signaling complex has been implicated in the pathology of
breast and prostate carcinoma. A multitude of pro-oncogenic intracellular signaling pathways are activated by
PRL in breast and prostate epithelial cells, leading to enhanced cellular proliferation, survival, and tumorigenesis
in numerous model systems. Emerging evidence suggests that targeting the PRL–PRLR axis in human
cancer may represent an unexploited avenue for therapeutic intervention and, given the extensive cross-talk
between PRLR and other signal transduction pathways, a potential means through which other anticancer
agents could be rendered more efficacious in the clinic. LFA102 is a potent anti-PRLR neutralizing antibody that
efficiently abrogates the function of this receptor in vivo, mediating significant antitumor effects in preclinical
models. The clean safety profile of this antibody in animals and in the clinical experiences to date suggests that
blocking the PRLR signaling pathway in human tumors may have few significant toxicologic consequences and
may be a promising approach to treating cancer. A phase I trial in patients with breast and prostate cancer is
underway to better understand the clinical utility of LFA102 and the contribution of PRL to the maintenance
and progression of human cancer.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/pubmed/?term...
Additional Information:	This is an invited review paper
Keywords:	LFA102, prolactin, prolactin receptor, breast cancer, prostate cancer
Related URLs:	http://www.ncbi.nlm.nih.gov/pubmed/?term...
Date Deposited:	13 Oct 2015 13:14
Last Modified:	13 Oct 2015 13:14
URI:	https://oak.novartis.com/id/eprint/8591