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Review

The prolactin receptor as a therapeutic target in human diseases: browsing new potential indications

& (Professor at University Pierre et Marie Curie, Head of the Adult Endocrinology Department at Hôpital Pitié Salpêtrière)
 

Abstract

Introduction: Prolactin (PRL) signaling has emerged as a relevant target in breast and prostate cancers. This has encouraged various laboratories to develop compounds targeting the PRL receptor (PRLR). As the latter is widely distributed, it is timely to address whether other conditions could also benefit from such inhibitors.

Areas covered: The authors briefly overview the two classes of PRLR blockers, which involve: i) PRL-core based analogs that have been validated as competitive antagonists in various preclinical models, and ii) anti-PRLR neutralizing antibodies that are currently in clinical Phase I for advanced breast and prostate cancers. The main purpose of this review is to discuss the multiple organs/diseases that may be considered as potential targets/indications for such inhibitors. This is done in light of reports suggesting that PRLR expression/signaling is increased in disease, and/or that systemic or locally elevated PRL levels correlate with (or promote) organ pathogenesis.

Expert opinion: The two immediate challenges in the field are i) to provide the scientific community with potent anti-prolactin receptor antibodies to map prolactin receptor expression in target organs, and ii) to take advantage of the availability of functionally validated PRLR blockers to establish the relevance of these potential indications in humans.

Acknowledgments

We apologize to all authors whose original work, due to space limitations, could not be cited in this review article. This Expert review comes after several years of discussion and fruitful collaborations with recognized experts in the different fields discussed in this paper to challenge Del1-9-G129R-hPRL antagonist in these pathophysiological contexts. We are grateful to all these collaborators, especially Marja Nevalainen (prostate cancer), Carrie Shemanko (breast cancer), Armen Akopian (pain), Ralf Paus (hair), Gunnar Norstedt (LAM), Jimena Ferraris and Thierry Brue (Pituitary), John Kopchick (strategy of antagonist development), Anne Reuwer, Menno Hoekstra and Marcel Twickler (atherosclerosis), and Isabelle Broutin, Birthe Kragelund and Patrick England for our long-standing partnership in structural/molecular studies of the PRL/PRLR interaction. From our lab, we wish to thank more specifically Paul Kelly, Zeina Chakhtoura, Lucila Sackmann Sala, Nicolas Barry Delongchamps, Jacques-Emmanuel Guidotti, Sophie Bernichtein, Vincent Rouet, Roman Bogorad, Chi Zhang, Estelle Tallet, Jean-Baptiste Jomain, Marta Llovera, Sandrina Kinet, Karima Kessal, Sabrina Hamdi, Florence Boutillon, Marie Bernadet and Christine Kayser for their contribution to the antagonist project. We also thank Charlotte Sumida for English proof-reading. This work was performed within the Département Hospitalo-Universitaire (DHU) AUToimmune and HORmonal diseaseS (AUTHORS).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

This box summarizes key points contained in the article.

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