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Neuroendocrine cells of prostate cancer: biologic functions and molecular mechanisms

Yu-Hua Huang1, Ya-Qun Zhang2, Jiao-Ti Huang3

  • 1Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.

Asian Journal of Andrology
|March 30, 2019
PubMed

Insights

Prostate cancer (PCa) treatment failure may involve neuroendocrine (NE) cells, which lack androgen receptors (AR) and can drive aggressive small-cell neuroendocrine carcinoma (SCNC) after therapy.

Area of Science:

  • Oncology
  • Urology
  • Cell Biology

Background:

  • Prostate cancer (PCa) is a significant health concern for aging men globally.
  • Current systemic therapies primarily target the androgen receptor (AR), but disease recurrence is common.
  • A subset of neuroendocrine (NE) cells within PCa, lacking AR expression, may contribute to treatment resistance and progression.

Purpose of the Study:

  • To review the histology of normal prostate and PCa, including adenocarcinoma and small-cell neuroendocrine carcinoma (SCNC).
  • To explore the molecular mechanisms underlying treatment failure, disease progression, and transformation from adenocarcinoma to SCNC.
  • To understand the role of NE cells in PCa development and therapeutic resistance.

Main Methods:

  • Systematic review of histology in normal prostate and PCa.
  • Analysis of findings from cellular and animal models of PCa.
  • Review of human specimen studies investigating PCa progression and transformation.

Main Results:

  • PCa histology includes AR-positive luminal cells and AR-negative NE cells.
  • NE cells are resistant to hormonal therapy and implicated in SCNC development.
  • Biomarkers like Rb, TP53, MYCN, and Aurora A kinase are associated with aggressive PCa and SCNC.

Conclusions:

  • Neuroendocrine cells play a critical role in prostate cancer treatment failure and transformation to aggressive SCNC.
  • Understanding NE cell biology is crucial for developing effective therapies for advanced prostate cancer.
  • Further research into biomarkers and molecular drivers is needed to combat PCa progression.
Keywords:
adenocarcinomaneuroendocrineprostatesmall-cell carcinoma

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