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Cellular plasticity and the neuroendocrine phenotype in prostate cancer

Alastair H Davies1,2, Himisha Beltran3, Amina Zoubeidi1,2

  • 1Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC, Canada.

Nature Reviews. Urology
|February 21, 2018
PubMed

Insights

Drug resistance in prostate cancer is driven by cells becoming neuroendocrine prostate cancer (NEPC). Understanding this lineage plasticity offers new therapeutic strategies for aggressive disease.

Area of Science:

  • Oncology
  • Cancer Biology
  • Cellular Reprogramming

Background:

  • Next-generation androgen receptor (AR) pathway inhibitors show limited success due to acquired drug resistance in prostate cancer.
  • Prostate cancer cells can acquire AR-independent growth pathways, leading to treatment failure.
  • A significant subset of resistant tumors exhibit neuroendocrine differentiation, forming aggressive neuroendocrine prostate cancer (NEPC).

Purpose of the Study:

  • To explore the link between cellular lineage plasticity and the development of neuroendocrine prostate cancer (NEPC).
  • To understand the mechanisms driving AR-independent growth and aggressive phenotypes in prostate cancer.
  • To identify novel therapeutic targets for treating advanced and resistant prostate cancer.

Main Methods:

  • Analysis of resistant prostate tumors with neuroendocrine features.
  • Investigation of cellular reprogramming and phenotypic switching in prostate cancer cells.
  • Examination of developmental programs associated with epithelial-mesenchymal plasticity and stem-like properties.

Main Results:

  • Acquired resistance in prostate cancer involves phenotypic changes towards AR-independent pathways.
  • Approximately 25% of resistant prostate tumors show cellular reprogramming towards NEPC.
  • NEPC tumors display reactivated developmental programs linked to plasticity and stem-cell characteristics.

Conclusions:

  • Lineage plasticity is a key driver in the emergence of aggressive neuroendocrine prostate cancer.
  • Understanding these plasticity mechanisms provides a basis for developing novel therapeutic strategies.
  • New knowledge on NEPC development can improve treatment and management of advanced prostate cancer.

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