ErbB-2 signaling in advanced prostate cancer progression and potential therapy

Endocr Relat Cancer. 2019 Apr 1;26(4):R195-R209. doi: 10.1530/ERC-19-0009.

Abstract

Currently, prostate cancer (PCa) remains the most commonly diagnosed solid tumor and the second leading cause of cancer-related deaths in US men. Most of these deaths are attributed to the development of castration-resistant (CR) PCa. ErbB-2 and ErbB family members have been demonstrated to contribute to the progression of this lethal disease. In this review, we focus on updating the role of ErbB-2 in advanced PCa progression and its regulation, including its regulation via ligand activation, miRNAs and protein phosphorylation. We also discuss its downstream signaling pathways, including AKT, ERK1/2 and STATs, involved in advanced PCa progression. Additionally, we evaluate the potential of ErbB-2, focusing on its protein hyper-phosphorylation status, as a biomarker for aggressive PCa as well as the effectiveness of ErbB-2 as a target for the treatment of CR PCa via a multitude of approaches, including orally available inhibitors, intratumoral expression of cPAcP, vaccination and immunotherapy.

Keywords: ErbB-2; castration-resistant prostate cancer; ErbB-2-targeting therapies; ErbB-2 regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Male
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Receptor, ErbB-2