Androgen receptor signaling pathways as a target for breast cancer treatment

Elisabetta Pietri, Vincenza Conteduca, Daniele Andreis, Ilaria Massa, Elisabetta Melegari, Samanta Sarti, Lorenzo Cecconetto, Alessio Schirone, Sara Bravaccini, Patrizia Serra, Anna Fedeli, Roberta Maltoni, Dino Amadori, Ugo De Giorgi, Andrea Rocca

Research output: Contribution to journalReview article

Abstract

The androgen receptor (AR) is a ligand-dependent transcription factor, and its effects on breast range from physiological pubertal development and age-related modifications to cancer onset and proliferation. The prevalence of AR in early breast cancer is around 60%, and AR is more frequently expressed in ER-positive than in ER-negative tumors. We offer an overview of AR signaling pathways in different breast cancer subtypes, providing evidence that its oncogenic role is likely to be different in distinct biological and clinical scenarios. In particular, in ER-positive breast cancer, AR signaling often antagonizes the growth stimulatory effect of ER signaling; in triple-negative breast cancer (TNBC), AR seems to drive tumor progression (at least in luminal AR subtype of TNBC with a gene expression profile mimicking luminal subtypes despite being negative to ER and enriched in AR expression); in HER2-positive breast cancer, in the absence of ER expression, AR signaling has a proliferative role. These data represent the rationale for AR-targeting treatment as a potentially new target therapy in breast cancer subset using androgen agonists in some AR-positive/ER-positive tumors, AR antagonists in triple-negative/ AR-positive tumors and in combination with anti-HER2 agents or with other signaling pathways inhibitors (including PI3K/MYC/ERK) in HER2-positive/AR-positive tumors. Only the ongoing and future prospective clinical trials will allow us to establish which agents are the best option in every specific condition, keeping in mind that there is evidence of opposite androgens and AR agonist/antagonist drug effects on cell proliferation particularly in AR-positive/ER-positive tumors.

Original languageEnglish
Pages (from-to)R485-R498
JournalEndocrine-Related Cancer
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

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Keywords

  • Androgen receptor
  • Androgen receptor structure
  • AR-targeting therapy
  • Breast cancer
  • Signaling pathway

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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