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

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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.

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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

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Acknowledgement

This work was supported in part by grants to CC from the NIH R01 CA69294, 92265, and 102682. Additional support to CC was also received from the Lynn Sage and Avon Foundations, and the Zell Scholar’s Fund.

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Authors and Affiliations

  1. Diana, Princess of Wales Professor of Cancer Research, Robert H. Lurie Comprehensive Cancer Center, Department of Pathology, Northwestern University, 4-107 Lurie Bldg., 303 E. Superior Street, Chicago, IL, 60611, USA

    Charles V. Clevenger

  2. Department of Pathology, Northwestern University, 4-107 Lurie Bldg., 303 E. Superior Street, Chicago, IL, 60611, USA

    Jiamao Zheng, Elizabeth M. Jablonski, Traci L. Galbaugh & Feng Fang

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  1. Charles V. Clevenger
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  2. Jiamao Zheng
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  3. Elizabeth M. Jablonski
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  4. Traci L. Galbaugh
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  5. Feng Fang
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Correspondence to Charles V. Clevenger.

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Clevenger, C.V., Zheng, J., Jablonski, E.M. et al. From Bench to Bedside: Future Potential for the Translation of Prolactin Inhibitors as Breast Cancer Therapeutics. J Mammary Gland Biol Neoplasia 13, 147–156 (2008). https://doi.org/10.1007/s10911-008-9074-8

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